中药调控Janus激酶/信号转导和转录激活因子(JAK/STAT)信号通路防治肝细胞癌的研究现状
DOI: 10.3969/j.issn.1001-5256.2023.11.030
Current research status of traditional Chinese medicine in the prevention and treatment of hepatocellular carcinoma by regulating the JAK/STAT signaling pathway
-
摘要: 肝细胞癌(HCC)是常见的消化道恶性肿瘤之一,因发病率高、恶性程度高、强侵袭与转移、预后差,严重威胁患者生命。目前HCC的主要防治手段有药物、手术及介入治疗等,但均存在一定的不良反应及副作用。Janus激酶/信号转导和转录活化因子(JAK/STAT)作为人体重要的细胞内信号转导通路,其主要通过调控细胞侵袭、转移、增殖、生长、凋亡、自噬、血管生成、炎症/免疫反应、铁代谢和药物耐药性等方面,发挥抗肝细胞癌效应。因此,靶向JAK/STAT信号通路对防治肝细胞癌的发生发展具有重要作用。中医药在HCC的治疗上具有多靶点、多途径、多成分、多层次的优势受到广泛关注,大量中医药治疗HCC的细胞或动物实验表明JAK/STAT信号通路是防治HCC的重要靶点,具有改善肝功能、减少HCC复发和提高免疫力等作用。基于此,本文通过梳理JAK/STAT信号通路在肝细胞癌中的作用机制,以及中药单体、中药提取物和中药复方对JAK/STAT信号通路的干预作用,以期为中医药防治肝细胞癌和临床新药研发给予理论依据和参考。Abstract: Hepatocellular carcinoma (HCC) is one of the common malignant tumors of the digestive tract and seriously threatens the life of patients due to a high incidence rate, a high degree of malignancy, strong invasion and metastasis, and poor prognosis. At present, the main methods for the prevention and treatment of HCC include drugs, surgery, and interventional treatment, but all of these methods have certain adverse reactions and side effects. As an important intracellular signal transduction pathway in the human body, the JAK/STAT signaling pathway mainly exerts an anti-HCC effect by regulating cell invasion, metastasis, proliferation, growth, apoptosis, autophagy, angiogenesis, inflammation/immune response, iron metabolism, and drug resistance. Therefore, targeting the JAK/STAT signaling pathway plays an important role in the prevention and treatment of the development and progression of HCC. Traditional Chinese medicine has attracted wide attention due to its advantages of multiple targets, pathways, components, and levels in the treatment of HCC, and many cell or animal experiments on traditional Chinese medicine in the treatment of HCC have shown that the JAK/STAT signaling pathway is an important target for the prevention and treatment of HCC, with the effects of improving liver function, reducing HCC recurrence, and improving immunity. Based on this, this article analyzes the mechanism of action of the JAK/STAT signaling pathway in HCC, as well as the intervention effect of traditional Chinese medicine monomers, traditional Chinese medicine extracts, and traditional Chinese medicine compounds on the JAK/STAT signaling pathway, in order to provide theoretical basis and reference for the prevention and treatment of HCC and the research and development of new traditional Chinese medicine drugs.
-
Key words:
- Carcinoma, Hepatocellular /
- Drugs, Chinese Herbal /
- Signal Transduction
-
表 1 中药活性成分及提取物靶向JAK/STAT信号通路调控HCC的作用机制
Table 1. The mechanism of action of traditional Chinese medicine active ingredients and extracts targeting the JAK/STAT signaling pathway to regulate HCC
类别 中药提取物 剂量 干预对象 作用机制 作用结果 参考文献 黄酮类 野黄芩苷 0.01、0.02、0.04 g/L MHCC97-H和HepG2细胞 上调p-JAK2、p-STAT3、JAK2和STAT3的mRNA,上调E-钙黏蛋白 抑制肝癌细胞增殖和侵袭 [43] 马鞭草总黄酮 50、100、200 mg/L HepG2细胞 下调IL-6、p-JAK2、p-STAT3 mRNA和JAK2、STAT3蛋白表达 抑制肝癌细胞增殖 [44] 荔枝核总黄酮 70、140、210 mg/L HepG2细胞 上调SHP-1和E-钙黏蛋白,下调JAK2、STAT3磷酸化和Vimentin 抑制肝癌细胞的增殖、迁移和侵袭,促进其凋亡 [45] 黑枸杞花青素 200 μg/mL HepG2细胞 下调JAK2、STAT3 mRNA和蛋白表达,上调LC3 基因和LC3-Ⅱ蛋白表达 促进肝癌细胞凋亡并增强细胞自噬 [46] 多糖类 黄芪多糖 200、300、400 mg/L SMMC-7721细胞 下调p-STAT3/STAT3和p-STAT5/STAT5的蛋白表达 抑制肝癌细胞迁移和侵袭 [47] 蒲公英多糖 24、48、72、96 mg/L HepG2和Huh7细胞 下调p-JAK2和p-STAT3以及铁调素的表达 调节肝癌细胞和移植肿瘤中的铁负荷 [48] 南瓜多糖 0.25、0.5、1.0 mg/kg HepG3细胞 下调STAT2、STAT3磷酸化和JAK活性 促进肝癌细胞凋亡 [49] 海参多糖 0、50、100、200 μg/mL HepG2细胞 下调JAK2、STAT3和survivin及其磷酸化水平 抑制肝癌细胞增殖,促进其凋亡 [50] 萜类 葫芦素E 0、10、20、40 nmol/L Huh7细胞 下调p-JAK3/JAK3、p-STAT3/STAT3比值及STAT3磷酸化和核易位 抑制肝癌细胞活力、增殖,诱导细胞周期停滞 [20] 葫芦素I 0.05、0.1、0.5、1.5 μmol/L HepG2细胞 下调STAT3和JAK2磷酸化水平,下调JAK2和STAT3基因的表达 抑制肝癌细胞活力、增殖。诱导细胞周期停滞 [51] 斑蝥素 0.1、0.2、0.4 mg/kg HepG2细胞 下调JAK2、STAT3磷酸化和STAT的核易位水平,下调EphB4的表达 抑制肝癌细胞生长,诱导细胞凋亡 [52] 苍耳亭 0、1、2.5、5、10、20 μmol/L HEK293和HepG2细胞 下调JAK1、TYK2和STAT3的磷酸化 抑制肝癌细胞生长 [53] 隐丹参酮 0.312 5、0.625、1.25、2.5、5、10、20 μg/mL Hepa1-6细胞系和EG7胸腺瘤细胞系 下调STAT3磷酸化和JAK2活性 抑制肝癌细胞增殖,促进其凋亡 [54] 青蒿素 100 mg/kg C57BL/6J小鼠 下调JAK2、STAT3磷酸化和Caspase-3表达 促进肝癌细胞凋亡 [55] 酚类 姜黄素 25 mg·kg·-1d-1 H22细胞 下调p-JAK1/2、p-STAT3蛋白和IL-6表达,上调抗炎细胞因子IL-4表达 抑制肝癌细胞生长和EMT,激活宿主免疫反应 [57] 丹皮酚 7.5、15、22.5、30、60 mg/L HepG2细胞 下调JAK1,JAK2,STAT3,STAT5蛋白表达 抑制肝癌细胞增殖,促进其凋亡 [58] 生物碱 荷包牡丹碱 5、10、25 μmol/L MHCC97-H细胞 下调VEGF、MMP-2、MMP-9基因表达及p-JAK2、p-STAT3蛋白表达 抑制肝癌细胞转移和侵袭 [59] 氧化槐果碱 2、4、8、16、32 mmol/L SMMC-7721细胞 下调STAT3、STAT5表达和抗凋亡Bal-2基因表达,上调促凋亡Bax基因表达 抑制肝癌细胞增殖,促进其凋亡 [60] 其他类 白花丹醌 0、1、2、4、8、10 μmol/L Huh-7和LM3细胞 下调N-钙黏蛋白、MMP-2、JAK和STAT蛋白表达,上调E-钙黏蛋白表达 抑制肝癌细胞的侵袭和迁移 [61] 蛇床子素 40、80、160 μmol/L HepG2细胞 下调N-钙黏蛋白、Vimentin、p-JAK/JAK和p-STAT3/STAT3蛋白表达,上调Bax/Bcl-2、Caspase-3和E-钙黏蛋白表达 抑制肝癌细胞增殖和侵袭,促进细胞凋亡 [62] 沙蟾毒精 5、10、20、40、80 nmol/L HepG2细胞 下调肿瘤免疫相关因子IL-8分泌水平,下调p-JAK、p-JAK2、p-STAT3蛋白表达 抑制肝癌细胞增殖,促进其凋亡 [63] 醉茄素A 2.5、5.0、10.0 μmol/L HepG2/ADM细胞 下调Bcl-2、p-JAK2和p-STAT3蛋白表达水平,上调Caspase-3蛋白表达 促进肝癌细胞凋亡 [64] 中药提取物 石榴皮提取物 0.5、1、1.5 μg/L HepG2细胞 下调JAK、STAT2、STAT3,上调PPAR-γ和Caspase-3 促进肝癌细胞凋亡 [65] 青蒿琥酯 25 mg/kg 雄性Wistar大鼠 下调IL-6、p-JAK2、p-STAT3(pY705)、Bcl-xL和Bcl-2的表达,上调Caspase-3和PARP和SOCS3 抑制肝癌细胞增殖,促进其凋亡 [66] 去甲斑蝥素 0、30、60、120 µmol/L HCCLM3和SMMC-7721细胞 下调N-钙黏蛋白、Vimentin、p-JAK2、p-STAT3和TWIET表达,上调E-钙黏蛋白 抑制肝癌细胞EMT [67] 苦参素注射液 0.75、1.5、3 mg/mL 人耐顺铂肝癌细胞株HepG2/DDP 下调p-JAK2/JAK2、p-STAT3/STAT3水平 增强顺铂化疗敏感性 [68] 表 2 中药复方靶向JAK/STAT信号通路调控HCC的作用机制
Table 2. The mechanism of action of traditional Chinese medicine compound targeting JAK/STAT signaling pathway to regulate HCC
中药复方 组成 剂量 干预对象 作用机制 作用结果 参考文献 芪楼丸 黄芪、重楼、女贞子、墨旱莲、莪术、白术等 6.75、13.5、27 g/kg HepG2细胞 上调Bax、Caspase-3和Caspase-9 的表达,下调Bcl-2、Bcl-2 mRNA表达和JAK2、STAT3、p-JAK2、p-STAT3、STAT5蛋白表达 抑制肝癌细胞增殖,促进其凋亡 [69] 茵陈蒿汤 茵陈、栀子、大黄 12.5、25、50 μg/mL HepG2细胞 下调p-JAK2、JAK2、p-STAT3和STAT3蛋白,下调Cyclin D1、c-Myc以及抗凋亡相关蛋白Mcl-1、Bcl-XL的表达 抑制肝癌细胞增殖,促进其凋亡 [70] 一贯煎 生地黄、麦冬、北沙参、枸杞、川楝子 11.5、23、46 g·kg·-1d-1 H22细胞 下调JAK1、STAT1磷酸化和c-Myc、Bal-2表达,上调p53基因 促进肝癌细胞凋亡 [71] 复方苦参注射液 苦参、白土茯苓 0.1 mg/L HepG2细胞 下调CyclinD1、c-Myc、Bcl-xL、MMP2、MMP9的表达量,下调p-JAK2及p-STAT3的表达 抑制肝癌细胞增殖和侵袭 [72] -
[1] SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71( 3): 209- 249. DOI: 10.3322/caac.21660. [2] DAI CM, JIN S, ZHANG JZ. Effect of Dahuang Zhechong Pills combined with TACE on VEGF, MMP-2, TGF-β1 and immune function of patients with primary liver cancer(blood stasis and collaterals blocking type)[J]. China J Chin Mater Med, 2021, 46( 3): 722- 729. DOI: 10.19540/j.cnki.cjcmm.20200716.501.戴朝明, 靳松, 张济周. 大黄蛰虫丸联合TACE术对原发性肝癌患者(瘀血阻络型)VEGF, MMP-2, TGF-β1及免疫功能的影响[J]. 中国中药杂志, 2021, 46( 3): 722- 729. DOI: 10.19540/j.cnki.cjcmm.20200716.501. [3] THOMAS SJ, SNOWDEN JA, ZEIDLER MP, et al. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours[J]. Br J Cancer, 2015, 113( 3): 365- 371. DOI: 10.1038/bjc.2015.233. [4] TANG JJH, HAO THNG DK, LIM JJ, et al. JAK/STAT signaling in hepatocellular carcinoma[J]. Hepat Oncol, 2020, 7( 1): HEP18. DOI: 10.2217/hep-2020-0001. [5] WANG JQ, HUANG Y. Role of the JAK-STAT signal pathway in the development and progression of liver cancer[J]. China Ind Econ, 2013, 21( 21): 2051- 2056.王建强, 黄缘. JAK-STAT信号通路在肝癌发生发展中作用的研究进展[J]. 世界华人消化杂志, 2013, 21( 21): 2051- 2056. [6] RAH B, RATHER RA, BHAT GR, et al. JAK/STAT signaling: Molecular targets, therapeutic opportunities, and limitations of targeted inhibitions in solid malignancies[J]. Front Pharmacol, 2022, 13: 821344. DOI: 10.3389/fphar.2022.821344. [7] XU XB, LAI YY, HUA ZC. Apoptosis and apoptotic body: Disease message and therapeutic target potentials[J]. Biosci Rep, 2019, 39( 1): BSR20180992. DOI: 10.1042/BSR20180992. [8] WANG X, DAI CY, YIN YF, et al. Blocking the JAK2/STAT3 and ERK pathways suppresses the proliferation of gastrointestinal cancers by inducing apoptosis[J]. J Zhejiang Univ Sci B, 2021, 22( 6): 492- 503. DOI: 10.1631/jzus.B2000842. [9] CUI ZQ, ZHANG YF. Effect of JAK-STAT signal transduction pathway blocker AG490 on the growth of xenograft tumor of hepatocellular carcinoma SMMC-7721 cells in nude mice[J]. Tumor, 2016, 36( 12): 1291- 1297.崔照琼, 张以芳. JAK-STAT信号转导通路阻断剂AG490对肝癌SMMC-7721细胞移植瘤生长的影响[J]. 肿瘤, 2016, 36( 12): 1291- 1297. [10] CAI LL, XIE Y, ZHANG XM, et al. Effect of LY294002 regulating JAK/STAT3 pathway on pro-liferation and apoptosis of hepatocarcinoma cells[J]. Chin J Curr Adv Gen Surg, 2022, 25( 5): 337- 342. DOI: 10.3969/j.issn.1009-9905.2022.05.001.蔡灵乐, 谢毅, 张新明, 等. LY294002调控JAK/STAT3通路对肝癌细胞增殖、凋亡的影响研究[J]. 中国现代普通外科进展, 2022, 25( 5): 337- 342. DOI: 10.3969/j.issn.1009-9905.2022.05.001. [11] FANG XY, ZHANG H, ZHAO L, et al. A new xanthatin analogue 1β-hydroxyl-5α-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma[J]. Biochimie, 2018, 152: 43- 52. DOI: 10.1016/j.biochi.2018.06.018. [12] WANG X, KHALIL RA. Matrix metalloproteinases, vascular remodeling, and vascular disease[J]. Adv Pharmacol, 2018, 81: 241- 330. DOI: 10.1016/bs.apha.2017.08.002. [13] FAN XX, JIN SX, LI YR, et al. Genetic and epigenetic regulation of E-cadherin signaling in human hepatocellular carcinoma[J]. Cancer Manag Res, 2019, 11: 8947- 8963. DOI: 10.2147/CMAR.S225606. [14] LIU XM, ZHU LY, WANG RR, et al. IFNγ inhibits fibroblast-leading tumor cell invasion through downregulating N-cadherin[J]. Biochem Biophys Res Commun, 2019, 512( 3): 544- 551. DOI: 10.1016/j.bbrc.2019.03.136. [15] HUANG LS, JIAN ZY, GAO Y, et al. RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways[J]. Aging, 2019, 11( 17): 6674- 6690. DOI: 10.18632/aging.102167. [16] SONG XY, MA JH. SRRM1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the JAK/STAT signaling pathway[J]. Tissue Cell, 2022, 79: 101954. DOI: 10.1016/j.tice.2022.101954. [17] MONTALTO FI, DE AMICIS F. Cyclin D1 in cancer: A molecular connection for cell cycle control, adhesion and invasion in tumor and stroma[J]. Cells, 2020, 9( 12): 2648. DOI: 10.3390/cells9122648. [18] XIE BW, WANG SY, JIANG N, et al. Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance[J]. Cancer Lett, 2019, 443: 56- 66. DOI: 10.1016/j.canlet.2018.11.019. [19] YIN YZ, ZHENG WH, ZHANG X, et al. LINC00346 promotes hepatocellular carcinoma progression via activating the JAK-STAT3 signaling pathway[J]. J Cell Biochem, 2020, 121( 1): 735- 742. DOI: 10.1002/jcb.29319. [20] LIU Y, YANG H, GUO Q, et al. Cucurbitacin E inhibits Huh7 hepatoma carcinoma cell proliferation and metastasis via suppressing MAPKs and JAK/STAT3 pathways[J]. Molecules, 2020, 25( 3): 560. DOI: 10.3390/molecules25030560. [21] JIANG QY, LIN ZL, SU ZW, et al. Peptide identification of hepatocyte growth-promoting factor and its function in cytoprotection and promotion of liver cell proliferation through the JAK2/STAT3/c-MYC pathway[J]. Eur J Pharmacol, 2022, 920: 174832. DOI: 10.1016/j.ejphar.2022.174832. [22] FRANCUZ T, CZAJKA-FRANCUZ P, CISOŃ-JUREK S, et al. The role of inflammation in colon cancer pathogenesis[J]. Postepy Hig Med Dosw(Online), 2016, 70: 360- 366. DOI: 10.5604/17322693.1200551. [23] LOKAU J, SCHOEDER V, HAYBAECK J, et al. Jak-stat signaling induced by interleukin-6 family cytokines in hepatocellular carcinoma[J]. Cancers, 2019, 11( 11): 1704. DOI: 10.3390/cancers11111704. [24] CHENG JT, DENG YN, YI HM, et al. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation[J]. Oncogenesis, 2016, 5( 2): e198. DOI: 10.1038/oncsis.2016.7. [25] SUN XX, SUI QJ, ZHANG C, et al. Targeting blockage of STAT3 in hepatocellular carcinoma cells augments NK cell functions via reverse hepatocellular carcinoma-induced immune suppression[J]. Mol Cancer Ther, 2013, 12( 12): 2885- 2896. DOI: 10.1158/1535-7163.MCT-12-1087. [26] APTE RS, CHEN DS, FERRARA N. VEGF in signaling and disease: Beyond discovery and development[J]. Cell, 2019, 176( 6): 1248- 1264. DOI: 10.1016/j.cell.2019.01.021. [27] XU JN, LIN HF, WU G, et al. IL-6/STAT3 is a promising therapeutic target for hepatocellular carcinoma[J]. Front Oncol, 2021, 11: 760971. DOI: 10.3389/fonc.2021.760971. [28] DONG D, FU Y, CHEN F, et al. Hyperoxia sensitizes hypoxic HeLa cells to ionizing radiation by downregulating HIF‑1α and VEGF expression[J]. Mol Med Rep, 2021, 23( 1): 62. DOI: 10.3892/mmr.2020.11700. [29] MENG YC, LOU XL, YANG LY, et al. Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: A meta-analysis[J]. J Cancer Res Clin Oncol, 2020, 146( 5): 1103- 1113. DOI: 10.1007/s00432-020-03174-1. [30] LIU DD, LIN JS, SU JR, et al. Glutamine deficiency promotes PCV2 infection through induction of autophagy via activation of ROS-mediated JAK2/STAT3 signaling pathway[J]. J Agric Food Chem, 2018, 66( 44): 11757- 11766. DOI: 10.1021/acs.jafc.8b04704. [31] ZHAO QH, WANG C, WANG KX, et al. Favorable prognostic role of IL-26 in HCC patients associated with JAK-STAT3-dependent autophagy[J]. Genes Dis, 2021, 9( 1): 9- 11. DOI: 10.1016/j.gendis.2021.08.002. [32] XU JY, ZHANG JR, MAO QF, et al. The interaction between autophagy and JAK/STAT3 signaling pathway in tumors[J]. Front Genet, 2022, 13: 880359. DOI: 10.3389/fgene.2022.880359. [33] RAH B, FARHAT NM, HAMAD M, et al. JAK/STAT signaling and cellular iron metabolism in hepatocellular carcinoma: Therapeutic implications[J]. Clin Exp Med, 2023. DOI: 10.1007/s10238-023-01047-8. [34] REN F, LI J, WANG YL, et al. The effects of Angelica sinensis polysaccharide on tumor growth and iron metabolism by regulating hepcidin in tumor-bearing mice[J]. Cell Physiol Biochem, 2018, 47( 3): 1084- 1094. DOI: 10.1159/000490185. [35] MILLER KJ, ASIM M. Unravelling the role of kinases that underpin androgen signalling in prostate cancer[J]. Cells, 2022, 11( 6): 952. DOI: 10.3390/cells11060952. [36] GAO AH, HU YR, ZHU WP. IFN-γ inhibits ovarian cancer progression via SOCS1/JAK/STAT signaling pathway[J]. Clin Transl Oncol, 2022, 24( 1): 57- 65. DOI: 10.1007/s12094-021-02668-9. [37] GHANDADI M, SAHEBKAR A. Interleukin-6: A critical cytokine in cancer multidrug resistance[J]. Curr Pharm Des, 2016, 22( 5): 518- 526. DOI: 10.2174/1381612822666151124234417. [38] XIE Y, ZHONG DW. AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1alpha/MDR-1 pathway[J]. EXCLI J, 2016, 15: 745- 757. DOI: 10.17179/excli2016-694. [39] CHEN WB, WU JH, SHI H, et al. Hepatic stellate cell coculture enables sorafenib resistance in Huh7 cells through HGF/c-Met/Akt and Jak2/Stat3 pathways[J]. Biomed Res Int, 2014, 2014: 764981. DOI: 10.1155/2014/764981. [40] ZHAO MY, ZHANG GL. Breakthrough points and difficulties in traditional Chinese medicine treatment of primary liver cancer[J]. J Clin Hepatol, 2021, 37( 9): 2016- 2024. DOI: 10.3969/j.issn.1001-5256.2021.09.004.钊梦媛, 张国梁. 中医药治疗原发性肝癌的切入点与难点[J]. 临床肝胆病杂志, 2021, 37( 9): 2016- 2024. DOI: 10.3969/j.issn.1001-5256.2021.09.004. [41] CHEN ZF, LIU Z, DENG TH, et al. Meta-analysis of clinical efficacy of traditional Chinese medicine in treating primary lung cancer[J]. Hunan J Tradit Chin Med, 2023, 39( 3): 124- 133. DOI: 10.16808/j.cnki.issn1003-7705.2023.03.031.谌泽芳, 刘珍, 邓天好, 等. 中药治疗原发性肝癌临床疗效的Meta分析[J]. 湖南中医杂志, 2023, 39( 3): 124- 133. DOI: 10.16808/j.cnki.issn1003-7705.2023.03.031. [42] LU DY, YE XW. Effect of Shenqi Huayu Formula combined with transcatheter arterial chemoembolization in the treatment of patients with primary hepatocellular carcinoma[J]. China Med Her, 2023, 20( 5): 98- 101, 110. DOI: 10.20047/j.issn1673-7210.2023.05.23.卢冬彦, 叶小卫. 参芪化瘀方联合经导管动脉化疗栓塞治疗原发性肝癌患者的效果[J]. 中国医药导报, 2023, 20( 5): 98- 101, 110. DOI: 10.20047/j.issn1673-7210.2023.05.23. [43] LIU K, TIAN T, ZHENG Y, et al. Scutellarin inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of JAK2/STAT3 pathway[J]. J Cell Mol Med, 2019, 23( 4): 3040- 3044. DOI: 10.1111/jcmm.14169. [44] LI YM, LI XJ. Effect of total flavonoids of Verbena officinalis on IL-6, JAK2, STAT3 level of human hepatocellular carcinoma HepG-2 cells[J]. J Henan Univ Sci Technol Med Sci, 2017, 35( 3): 169- 171. DOI: 10.15926/j.cnki.issn1672-688x.2017.03.003.李永明, 李先佳. 马鞭草总黄酮对肝癌HepG-2细胞IL-6、JAK2、STAT3水平的影响[J]. 河南科技大学学报(医学版), 2017, 35( 3): 169- 171. DOI: 10.15926/j.cnki.issn1672-688x.2017.03.003. [45] LI MH, MA XC, TANG Y, et al. Effect of total flavone of Litchi Semen on proliferation, migration, and invasion of HepG2 cells based on JAK2/STAT3 signaling pathway[J]. Chin J Exp Tradit Med Formulae, 2022, 28( 22): 85- 92. DOI: 10.13422/j.cnki.syfjx.20221522.黎敏航, 马晓聪, 唐燕, 等. 基于JAK2/STAT3信号通路探讨荔枝核总黄酮对HepG2增殖、迁移与侵袭的影响[J]. 中国实验方剂学杂志, 2022, 28( 22): 85- 92. DOI: 10.13422/j.cnki.syfjx.20221522. [46] LIU JH, WANG MJ, ZHANG LF, et al. Effects of Anthocyanins from Lycium ruthenicum Murr on the interaction between apoptosis and autophagy of human hepatoma HepG2 cells[J]. J Qinghai Univ, 2022, 40( 3): 54- 59. DOI: 10.13901/j.cnki.qhwxxbzk.2022.03.009.刘嘉华, 王梦杰, 张龙飞, 等. 黑果枸杞花青素对人肝癌HepG2细胞凋亡与自噬相互作用的影响[J]. 青海大学学报, 2022, 40( 3): 54- 59. DOI: 10.13901/j.cnki.qhwxxbzk.2022.03.009. [47] XU F, AN TZ, PIAO SH, et al. Effects of Astragalus Polysaccharide on invasion and metastasis of hepatocellular carcinoma cell line SMMC-7721 via Janus kinase/signal transducer and activator of tranions signaling pathway[J]. Chin J Clin Pharmacol, 2020, 36( 11): 1499- 1502. DOI: 10.13699/j.cnki.1001-6821.2020.11.026.徐放, 安铁洙, 朴善花, 等. 黄芪多糖通过Janus激酶/信号转导与转录激活子信号通路对肝癌细胞SMMC-7721侵袭和转移的影响[J]. 中国临床药理学杂志, 2020, 36( 11): 1499- 1502. DOI: 10.13699/j.cnki.1001-6821.2020.11.026. [48] REN F, YANG YY, WU KX, et al. The effects of dandelion polysaccharides on iron metabolism by regulating hepcidin via JAK/STAT signaling pathway[J]. Oxid Med Cell Longev, 2021, 2021: 7184760. DOI: 10.1155/2021/7184760. [49] SHEN WX, CHEN CH, GUAN YY, et al. A pumpkin polysaccharide induces apoptosis by inhibiting the JAK2/STAT3 pathway in human hepatoma HepG2 cells[J]. Int J Biol Macromol, 2017, 104( Pt A): 681- 686. DOI: 10.1016/j.ijbiomac.2017.06.078. [50] LU ZH, BAI YQ, SUN CY, et al. Effects of sea cucumber polysaccharide regulating JAK2/STAT3/survivin pathway on proliferation and apoptosis of hepatocellular carcinoma cells[J]. Chin J Bases Clin Gen Surg, 2022, 29( 7): 875- 880.卢战辉, 白阳秋, 孙趁意, 等. 海参多糖调控JAK2/STAT3/survivin通路对肝癌细胞增殖和凋亡的影响[J]. 中国普外基础与临床杂志, 2022, 29( 7): 875- 880. [51] ÜREMIŞ N, ÜREMIŞ MM, ÇIĞREMIŞ Y, et al. Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK/STAT3, MAPK/ERK, and AKT/mTOR signaling pathways in HepG2 cell line[J]. J Food Biochem, 2022, 46( 10): e14333. DOI: 10.1111/jfbc.14333. [52] ZHU M, SHI XP, GONG ZY, et al. Cantharidin treatment inhibits hepatocellular carcinoma development by regulating the JAK2/STAT3 and PI3K/Akt pathways in an EphB4-dependent manner[J]. Pharmacol Res, 2020, 158: 104868. DOI: 10.1016/j.phrs.2020.104868. [53] LIU M, XIAO CQ, SUN MW, et al. Xanthatin inhibits STAT3 and NF-κB signalling by covalently binding to JAK and IKK kinases[J]. J Cell Mol Med, 2019, 23( 6): 4301- 4312. DOI: 10.1111/jcmm.14322. [54] HAN Z, LIU S, LIN HS, et al. Inhibition of murine hepatoma tumor growth by cryptotanshinone involves TLR7-dependent activation of macrophages and induction of adaptive antitumor immune defenses[J]. Cancer Immunol Immunother, 2019, 68( 7): 1073- 1085. DOI: 10.1007/s00262-019-02338-4. [55] GUO JP, GUO B, LI LL, et al. Effect of artemisinin inhibiting JAK2/STAT3 pathway on apoptosis of hepatocellular carcinoma cells[J]. J Shanxi Med Univ, 2017, 48( 2): 97- 100. DOI: 10.13753/j.issn.1007-6611.2017.02.001.郭佳培, 郭彬, 李雷雷, 等. 青蒿素通过抑制JAK2/STAT3信号通路诱导肝癌细胞凋亡[J]. 山西医科大学学报, 2017, 48( 2): 97- 100. DOI: 10.13753/j.issn.1007-6611.2017.02.001. [56] ZHAO T, WANG ZJ, WEI XJ, et al. Research progress in biological activities of flavonoids[J]. Transl Med J, 2023, 12( 3): 210- 214. DOI: 10.3969/j.issn.2095-3097.2023.03.017.赵彤, 王姿婧, 魏秀娟, 等. 黄酮类化合物生物活性研究进展[J]. 转化医学杂志, 2023, 12( 3): 210- 214. DOI: 10.3969/j.issn.2095-3097.2023.03.017. [57] MAN SL, YAO JW, LV PP, et al. Curcumin-enhanced antitumor effects of sorafenib via regulating the metabolism and tumor microenvironment[J]. Food Funct, 2020, 11( 7): 6422- 6432. DOI: 10.1039/c9fo01901d. [58] YU YY, LIANG MH. Effects of paeonol on proliferation and apoptosis of hepatocellular carcinoma cells and JAK-STAT signaling pathway[J]. Chin J Gerontol, 2017, 37( 7): 1591- 1593. DOI: 10.3969/j.issn.1005-9202.2017.07.011.于洋洋, 梁明辉. 丹皮酚对肝癌细胞增殖凋亡及JAK-STAT信号通路的影响[J]. 中国老年学杂志, 2017, 37( 7): 1591- 1593. DOI: 10.3969/j.issn.1005-9202.2017.07.011. [59] GUO M, ZHANG CH, WU TT. Effects of dicentrine on migration and invasion of human hepatocellular carcinoma MHCC97-H cells and potential mechanisms[J]. Chin Tradit Herb Drugs, 2019, 50( 22): 5515- 5520. DOI: 10.7501/j.issn.0253-2670.2019.22.019.郭锰, 张成辉, 吴婷婷. 荷包牡丹碱对人肝癌MHCC97-H细胞转移、侵袭的影响及机制研究[J]. 中草药, 2019, 50( 22): 5515- 5520. DOI: 10.7501/j.issn.0253-2670.2019.22.019. [60] XIE JJ, WANG QH, XIA XH, et al. Effects of oxysophocarpine on proliferation and apoptosis of hepatocellular carcinoma SMMC-7721 cells[J]. Chin J Clin Res, 2019, 32( 6): 826- 829. DOI: 10.13429/j.cnki.cjcr.2019.06.027.谢俊杰, 王庆华, 夏晓华, 等. 氧化槐果碱对肝癌SMMC-7721细胞增殖与凋亡的影响[J]. 中国临床研究, 2019, 32( 6): 826- 829. DOI: 10.13429/j.cnki.cjcr.2019.06.027. [61] CHENG T, WEI YF, LIU H, et al. Effects of plumbagin on migration and invasion of human hepatoma cell line via JAK2/STAT3 signaling pathway[J]. J Hainan Med Univ, 2023, 29( 1): 36- 44. DOI: 10.13210/j.cnki.jhmu.20221110.002.成桃, 韦燕飞, 刘欢, 等. 基于JAK2/STAT3信号通路探讨白花丹醌对人肝癌细胞迁移和侵袭的影响[J]. 海南医学院学报, 2023, 29( 1): 36- 44. DOI: 10.13210/j.cnki.jhmu.20221110.002. [62] LONG XX, YANG W, FAN DD, et al. Osthole inhibiting the progress of liver cancer in vivo and vitro by JAK/STAT3 signaling pathway[J]. Chin J Integr Tradit West Med Liver Dis, 2022, 32( 9): 825- 830. DOI: 10.3969/j.issn.1005-0264.2022.09.014.龙晓霞, 杨伟, 范丹丹, 等. 蛇床子素对肝癌HepG细胞增殖、凋亡、侵袭能力的影响[J]. 中西医结合肝病杂志, 2022, 32( 9): 825- 830. DOI: 10.3969/j.issn.1005-0264.2022.09.014. [63] KONG LQ, QIAN HS, LI SH, et al. Regulatory effects of arenobufagin on proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells and the mechanism[J]. Shandong Med J, 2022, 62( 20): 6- 10. DOI: 10.3969/j.issn.1002-266X.2022.20.002.孔令麒, 钱海珊, 李绍花, 等. 沙蟾毒精对人肝癌细胞HepG2增殖凋亡的调控作用及其机制[J]. 山东医药, 2022, 62( 20): 6- 10. DOI: 10.3969/j.issn.1002-266X.2022.20.002. [64] ZHANG Y, ZHAO KX, ZHANG L. Effect of withaferin A on apoptosis of HepG2/ADM cells through JAK/STAT pathway[J]. Drugs Clin, 2020, 35( 4): 641- 646. DOI: 10.7501/j.issn.1674-5515.2020.04.008.张阳, 赵柯心, 张磊. 醉茄素A通过JAK/STAT通路对人肝癌耐药细胞HepG2/ADM凋亡的影响[J]. 现代药物与临床, 2020, 35( 4): 641- 646. DOI: 10.7501/j.issn.1674-5515.2020.04.008. [65] ELBAKRY MMM, ELBAKARY NM, HAGAG SA, et al. Pomegranate peel extract sensitizes hepatocellular carcinoma cells to ionizing radiation, induces apoptosis and inhibits MAPK, JAK/STAT3, β-catenin/NOTCH, and SOCS3 signaling[J]. Integr Cancer Ther, 2023, 22: 15347354221151021. DOI: 10.1177/15347354221151021. [66] ILAMATHI M, PRABU PC, AYYAPPA KA, et al. Artesunate obliterates experimental hepatocellular carcinoma in rats through suppression of IL-6-JAK-STAT signalling[J]. Biomed Pharmacother, 2016, 82: 72- 79. DOI: 10.1016/j.biopha.2016.04.061. [67] GAO YB, LI WD, LIU R, et al. Norcantharidin inhibits IL-6-induced epithelial‑mesenchymal transition via the JAK2/STAT3/TWIST signaling pathway in hepatocellular carcinoma cells[J]. Oncol Rep, 2017, 38( 2): 1224- 1232. DOI: 10.3892/or.2017.5775. [68] CHEN FS, HUANG XH. Effect of matrine on the sensitivity of human hepatoma cells to cisplatin[J]. Biotechnology, 2022, 32( 2): 188- 194. DOI: 10.16519/j.cnki.1004-311x.2022.02.0030.陈丰穗, 黄兴华. 苦参素对人肝癌细胞顺铂敏感性的影响[J]. 生物技术, 2022, 32( 2): 188- 194. DOI: 10.16519/j.cnki.1004-311x.2022.02.0030. [69] KANG L, LI B, WANG XD, et al. Effects of Qilou Pills on proliferation and apoptosis of human hepatoma HepG2 cells via JAK/STAT signaling pathway[J]. Chin Tradit Pat Med, 2023, 45( 2): 429- 434. DOI: 10.3969/j.issn.1001-1528.2023.02.014.康莉, 李波, 王晓栋, 等. 芪楼丸通过调控JAK/STAT信号通路对人肝癌HepG2细胞增殖与凋亡的影响[J]. 中成药, 2023, 45( 2): 429- 434. DOI: 10.3969/j.issn.1001-1528.2023.02.014. [70] TAN ZB, DING WJ, XU YC, et al. Yinchenhao Decoction regulate proliferation and apoptosis in hepatocellular carcinoma by JAK2/STAT3 signaling pathway[J]. Mod Digest Interv, 2021, 26( 3): 295- 299. DOI: 10.3969/j.issn.1672-2159.2021.03.003.谭章斌, 丁文俊, 徐由财, 等. 茵陈蒿汤抑制JAK2/STAT3信号通路调控肝癌细胞增殖与凋亡[J]. 现代消化及介入诊疗, 2021, 26( 3): 295- 299. DOI: 10.3969/j.issn.1672-2159.2021.03.003. [71] XIE B, XIE X, RAO B, et al. Effect of yiguanjian on JAK1/STAT1 signaling pathway and expression of downstream apoptosis related proteins in liver cancer[J]. Chin J Exp Tradit Med Formulae, 2017, 23( 18): 100- 104. DOI: 10.13422/j.cnki.syfjx.2017180100.谢斌, 谢雄, 饶斌, 等. 一贯煎对肝癌JAK1/STAT1信号通路及其下游凋亡相关蛋白表达的影响[J]. 中国实验方剂学杂志, 2017, 23( 18): 100- 104. DOI: 10.13422/j.cnki.syfjx.2017180100. [72] ZHANG DW, ZHANG HG, WANG LL, et al. Regulation of compound Sophora flavescens injection on proliferation and invasion of HepG2 cells via JAK2/STAT3 signaling pathway[J]. J Hepatobiliary Surg, 2020, 28( 2): 145- 148. DOI: 10.3969/j.issn.1006-4761.2020.02.019.张大为, 张海光, 王丽莉, 等. 复方苦参注射液通过JAK2/STAT3信号通路对肝癌HepG2细胞增殖、侵袭的调控作用[J]. 肝胆外科杂志, 2020, 28( 2): 145- 148. DOI: 10.3969/j.issn.1006-4761.2020.02.019.
计量
- 文章访问数: 485
- HTML全文浏览量: 300
- PDF下载量: 30
- 被引次数: 0