中药活性成分调控糖代谢抗胆管癌的分子机制

赵方言; 李姗; 王祥麒; 尹怡

doi:10.12449/JCH240832

中药活性成分调控糖代谢抗胆管癌的分子机制

DOI: 10.12449/JCH240832

赵方言^1a,
李姗^1b,
王祥麒^2, , ,,
尹怡²

1a.
河南中医药大学第三临床医学院，郑州 450046
1b.
河南中医药大学医学院，郑州 450046
2.
河南中医药大学第三附属医院肿瘤科，郑州 450046

基金项目:

河南省中医药科学研究专项课题 (2023ZY2110);

河南省高等学校青年骨干教师资助项目 (2021GGJS084)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：赵方言负责资料分析，论文撰写；尹怡检索文献，收集数据；李姗、王祥麒负责拟定写作思路，修改论文及最后定稿。

详细信息

通信作者:
王祥麒， wangxiangqi777@163.com （ORCID： 0009-0000-9120-1702）

计量
- 文章访问数: 106
- HTML全文浏览量: 281
- PDF下载量: 15
- 被引次数: 0
出版历程
- 收稿日期: 2024-01-10
- 录用日期: 2024-02-01
- 出版日期: 2024-08-25

Molecular mechanism of traditional Chinese medicine active components in regulating glucose metabolism against cholangiocarcinoma

Fangyan ZHAO^1a,
Shan LI^1b,
Xiangqi WANG^{2
, ,
,},
Yi YIN²

1a.
The Third Clinical Medical College，Henan University of Chinese Medicine，Zhengzhou 450046，China
1b.
School of Medicine，Henan University of Chinese Medicine，Zhengzhou 450046，China
2.
Department of Oncology，The Third Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450046，China

Research funding:

The Special Project for Scientific Research on Traditional Chinese Medicine in Henan Province (2023ZY2110);

The Training Program for Young Scholars in Universities of Henan Province (2021GGJS084)

More Information

Corresponding author: WANG Xiangqi， wangxiangqi777@163.com （ORCID： 0009-0000-9120-1702）

摘要

摘要: 胆管癌是一种高度异质性的肿瘤，其发病隐匿、病情凶险、恶性程度高、预后极差。葡萄糖是胆管癌增殖和转移的主要能量来源，胆管癌细胞在快速增殖过程中其糖代谢途径会被重新编辑，产生大量能量以满足自身需求。中医药在胆管癌治疗中具有独特优势，中药活性成分已被证明可以通过调控糖代谢抑制胆管癌的发生和发展。本文对胆管癌中的糖代谢特点和中药活性成分调控糖代谢抗胆管癌进行综述，为胆管癌的治疗提供新思路。
- 胆管肿瘤 /
- 碳水化合物代谢 /
- 中药 /
- 药理作用分子作用机制（中药）
Abstract: Cholangiocarcinoma is a highly heterogeneous tumor with an insidious onset， severe conditions， a high degree of malignancy， and an extremely poor prognosis. Glucose is a major energy source for the proliferation and metastasis of cholangiocarcinoma， and the glucose metabolism pathway of cholangiocarcinoma cells will be re-edited in the process of rapid proliferation to produce a large amount of energy for their own needs. Traditional Chinese medicine has unique advantages in the treatment of cholangiocarcinoma， and studies have shown that the active components of traditional Chinese medicine can inhibit the development and progression of cholangiocarcinoma by regulating glucose metabolism. This article reviews the characteristics of glucose metabolism in cholangiocarcinoma and the role of the active components of traditional Chinese medicine in regulating glucose metabolism against cholangiocarcinoma， in order to provide new ideas for the treatment of cholangiocarcinoma.
- Bile Duct Neoplasms /
- Carbohydrate Metabolism /
- Traditional Chinese Drugs /
- Molecular Mechanisms of Pharmacological Action （TCD）

HTML全文

参考文献(44)

[1]	Chinese Chapter of International Hepato-Pancreato-Biliary Association; Hepatic Surgery Group, Chinese Society of Surgery, Chinese Medical Association. Diagnosis and treatment of cholangiocarcinoma: Surgical expert consensus[J]. J Clin Hepatol, 2015, 31( 1): 12- 16. DOI: 10.3969/j.issn.1001-5256.2015.01.003. 国际肝胆胰学会中国分会, 中华医学会外科学分会肝脏外科学组. 胆管癌诊断与治疗——外科专家共识[J]. 临床肝胆病杂志, 2015, 31( 1): 12- 16. DOI: 10.3969/j.issn.1001-5256.2015.01.003.
[2]	BANALES JM, MARIN JJG, LAMARCA A, et al. Cholangiocarcinoma 2020: The next horizon in mechanisms and management[J]. Nat Rev Gastroenterol Hepatol, 2020, 17( 9): 557- 588. DOI: 10.1038/s41575-020-0310-z.
[3]	RIZVI S, KHAN SA, HALLEMEIER CL, et al. Cholangiocarcinoma—Evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol, 2018, 15: 95- 111. DOI: 10.1038/nrclinonc.2017.157.
[4]	BLECHACZ B, GORES GJ. Cholangiocarcinoma: Advances in pathogenesis, diagnosis, and treatment[J]. Hepatology, 2008, 48( 1): 308- 321. DOI: 10.1002/hep.22310.
[5]	HOWELL M, VALLE JW. The role of adjuvant chemotherapy and radiotherapy for cholangiocarcinoma[J]. Best Pract Res Clin Gastroenterol, 2015, 29( 2): 333- 343. DOI: 10.1016/j.bpg.2015.03.001.
[6]	VALERO V 3, COSGROVE D, HERMAN JM, et al. Management of perihilar cholangiocarcinoma in the era of multimodal therapy[J]. Expert Rev Gastroenterol Hepatol, 2012, 6( 4): 481- 495. DOI: 10.1586/egh.12.20.
[7]	GLAZER ES, LIU P, ABDALLA EK, et al. Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins[J]. J Gastrointest Surg, 2012, 16( 9): 1666- 1671. DOI: 10.1007/s11605-012-1935-1.
[8]	RAGGI C, TADDEI ML, RAE C, et al. Metabolic reprogramming in cholangiocarcinoma[J]. J Hepatol, 2022, 77( 3): 849- 864. DOI: 10.1016/j.jhep.2022.04.038.
[9]	CHEN XY, DONG Q, TIAN SD, et al. Comment on the clinical value of traditional Chinese medicine in the maintenance treatment of tumor[J]. J Beijing Univ Tradit Chin Med, 2021, 44( 9): 777- 783. DOI: 10.3969/j.issn.1006-2157.2021.09.002. 陈信义, 董青, 田劭丹, 等. 恶性肿瘤中医药维持治疗临床价值与述评[J]. 北京中医药大学学报, 2021, 44( 9): 777- 783. DOI: 10.3969/j.issn.1006-2157.2021.09.002.
[10]	CHEN HB, ZHOU HG, LI L, et al. Thoughts on the development of TCM oncology[J]. Chin J Inf Tradit Chin Med, 2019, 26( 11): 1- 4. DOI: 10.3969/j.issn.1005-5304.2019.11.001. 陈海彬, 周红光, 李黎, 等. 中医肿瘤学科发展思考[J]. 中国中医药信息杂志, 2019, 26( 11): 1- 4. DOI: 10.3969/j.issn.1005-5304.2019.11.001.
[11]	CHEN Y, JIANG Y, YANG H, et al. Research progress of anti-tumor traditional Chinese medicine ingredients regulating key enzymes of aerobic glycolysis pathway[J]. Chin J Oncol Prev Treat, 2020, 12( 6): 705- 709. DOI: 10.3969/j.issn.1674-5671.2020.06.20. 陈亚, 江圆, 杨浩, 等. 调控有氧糖酵解途径关键酶的抗肿瘤中药成分的研究进展[J]. 中国癌症防治杂志, 2020, 12( 6): 705- 709. DOI: 10.3969/j.issn.1674-5671.2020.06.20.
[12]	LI XY, BIAN K. Research progress on intervention of Chinese material medical on cancer Warburg effect[J]. Acta Univ Tradit Med Sin Pharmacol Shanghai, 2017, 31( 1): 87- 99. DOI: 10.16306/j.1008-861x.2017.01.020. 李晓芸, 卞卡. 中药干预肿瘤Warburg效应的研究进展[J]. 上海中医药大学学报, 2017, 31( 1): 87- 99. DOI: 10.16306/j.1008-861x.2017.01.020.
[13]	WU QX, SUN MY, XU B, et al. Research progress of Chinese medicine intervention on metabolism reprogramming for anti-tumor[J]. Acad J Shanghai Univ Tradit Chin Med, 2020, 34( 2): 94- 100. DOI: 10.16306/j.1008-861x.2020.02.017. 吴秋雪, 孙梦瑶, 许博, 等. 中药干预代谢重编程抗肿瘤研究进展[J]. 上海中医药大学学报, 2020, 34( 2): 94- 100. DOI: 10.16306/j.1008-861x.2020.02.017.
[14]	ANCEY PB, CONTAT C, MEYLAN E. Glucose transporters in cancer- from tumor cells to the tumor microenvironment[J]. FEBS J, 2018, 285( 16): 2926- 2943. DOI: 10.1111/febs.14577.
[15]	PAUDYAL B, ORIUCHI N, PAUDYAL P, et al. Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using[¹⁸F]-2-fluro-2-deoxy-d-glucose positron emission tomography[J]. Cancer Sci, 2008, 99( 2): 260- 266. DOI: 10.1111/j.1349-7006.2007.00683.x.
[16]	KUBO Y, AISHIMA S, TANAKA Y, et al. Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma[J]. Hum Pathol, 2014, 45( 8): 1610- 1617. DOI: 10.1016/j.humpath.2014.03.008.
[17]	LI X, YU C, LUO YC, et al. Aldolase A enhances intrahepatic cholangiocarcinoma proliferation and invasion through promoting glycolysis[J]. Int J Biol Sci, 2021, 17( 7): 1782- 1794. DOI: 10.7150/ijbs.59068.
[18]	THAMRONGWARANGGOON U, SEUBWAI W, PHOOMAK C, et al. Targeting hexokinase II as a possible therapy for cholangiocarcinoma[J]. Biochem Biophys Res Commun, 2017, 484( 2): 409- 415. DOI: 10.1016/j.bbrc.2017.01.139.
[19]	MAZUREK S. Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells[J]. Int J Biochem Cell Biol, 2011, 43( 7): 969- 980. DOI: 10.1016/j.biocel.2010.02.005.
[20]	QIAN Z, HU WD, LV Z, et al. PKM2 upregulation promotes malignancy and indicates poor prognosis for intrahepatic cholangiocarcinoma[J]. Clin Res Hepatol Gastroenterol, 2020, 44( 2): 162- 173. DOI: 10.1016/j.clinre.2019.06.008.
[21]	YU YP, LIAO MQ, LIU RW, et al. Overexpression of lactate dehydrogenase-a in human intrahepatic cholangiocarcinoma: Its implication for treatment[J]. World J Surg Oncol, 2014, 12( 1): 78. DOI: 10.1186/1477-7819-12-78.
[22]	THONSRI U, SEUBWAI W, WARAASAWAPATI S, et al. Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated with poor prognosis[J]. Histol Histopathol, 2017, 32( 5): 503- 510. DOI: 10.14670/HH-11-819.
[23]	CHEN MZ, LI YL, TANG LK, et al. Research progress in IDH1 mutation in treatment of intrahepatic cholangiocarcinoma[J/OL]. Chin J Hepat Surg: Electronic Edition, 2024, 13( 1): 103- 108. DOI: 10.3877/cma.j.issn.2095-3232.2024.01.021. 陈明政, 栗玉龙, 唐流康, 等. IDH1突变应用于肝内胆管癌治疗的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13( 1): 103- 108. DOI: 10.3877/cma.j.issn.2095-3232.2024.01.021.
[24]	WU MJ, SHI L, MERRITT J, et al. Biology of IDH mutant cholangiocarcinoma[J]. Hepatology, 2022, 75( 5): 1322- 1337. DOI: 10.1002/hep.32424.
[25]	CHEN X, YANG PP, QIAO Y, et al. Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2[J]. Sci Rep, 2022, 12: 18830. DOI: 10.1038/s41598-022-23659-y.
[26]	LI D, WANG CQ, MA PF, et al. PGC1α promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect[J]. Cell Death Dis, 2018, 9( 5): 466. DOI: 10.1038/s41419-018-0494-0.
[27]	PANT K, RICHARD S, PEIXOTO E, et al. Role of glucose metabolism reprogramming in the pathogenesis of cholangiocarcinoma[J]. Front Med(Lausanne), 2020, 7: 113. DOI: 10.3389/fmed.2020.00113.
[28]	RAGGI C, TADDEI ML, SACCO E, et al. Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma[J]. J Hepatol, 2021, 74( 6): 1373- 1385. DOI: 10.1016/j.jhep.2020.12.031.
[29]	GIACOMINI I, RAGAZZI E, PASUT G, et al. The pentose phosphate pathway and its involvement in cisplatin resistance[J]. Int J Mol Sci, 2020, 21( 3): 937. DOI: 10.3390/ijms21030937.
[30]	YANG HC, WU YH, YEN WC, et al. The redox role of G6PD in cell growth, cell death, and cancer[J]. Cells, 2019, 8( 9): 1055. DOI: 10.3390/cells8091055.
[31]	QU XZ, SHENG JY, SHEN LY, et al. Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS[J]. PLoS One, 2017, 12( 3): e0173712. DOI: 10.1371/journal.pone.0173712.
[32]	ZHAO W, YANG SZ, CHEN JF, et al. Forced overexpression of FBP1 inhibits proliferation and metastasis in cholangiocarcinoma cells via Wnt/β-catenin pathway[J]. Life Sci, 2018, 210: 224- 234. DOI: 10.1016/j.lfs.2018.09.009.
[33]	ZHOU ZL, YANG YX, DING J, et al. Triptolide: Structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms[J]. Nat Prod Rep, 2012, 29( 4): 457. DOI: 10.1039/c2np00088a.
[34]	LI L, WANG CT, QIU ZP, et al. Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway[J]. Phytomedicine, 2023, 109: 154575. DOI: 10.1016/j.phymed.2022.154575.
[35]	ANDÚJAR I, RECIO MC, GINER RM, et al. Traditional Chinese medicine remedy to jury: The pharmacological basis for the use of shikonin as an anticancer therapy[J]. Curr Med Chem, 2013, 20( 23): 2892- 2898. DOI: 10.2174/09298673113209990008.
[36]	THONSRI U, SEUBWAI W, WARAASAWAPATI S, et al. Antitumor effect of shikonin, a PKM2 inhibitor, in cholangiocarcinoma cell lines[J]. Anticancer Res, 2020, 40( 9): 5115- 5124. DOI: 10.21873/anticanres.14515.
[37]	LAI LJ, XIE JL, HUANG ZH. Progress in pharmacological effects of icaritin[J]. Pharmacol Clin Chin Mater Med, 2016, 32( 6): 235- 238. DOI: 10.13412/j.cnki.zyyl.2016.06.068. 赖丽娟, 谢佳丽, 黄志华. 淫羊藿素的抗肿瘤作用及机制研究进展[J]. 中药药理与临床, 2016, 32( 6): 235- 238. DOI: 10.13412/j.cnki.zyyl.2016.06.068.
[38]	DENG DJ, LI L, TAN XY, et al. Effect and mechanism of icaritin on inhibiting proliferation of intrahepatic cholangiocarcinoma cells by Akt/mTOR-mediated glycolysis[J]. Chin Tradit Herb Drugs, 2022, 53( 10): 3061- 3069. DOI: 10.7501/j.issn.0253-2670.2022.10.016. 邓冬杰, 李励, 谈相云, 等. 淫羊藿素通过Akt/mTOR调控糖酵解抑制肝内胆管癌细胞增殖的作用机制研究[J]. 中草药, 2022, 53( 10): 3061- 3069. DOI: 10.7501/j.issn.0253-2670.2022.10.016.
[39]	CHEN C, XIE YY, HUANG LP. Advance of pharmacological studies on nuciferine[J]. J Nanjing Univ Tradit Chin Med, 2021, 37( 4): 619- 624. DOI: 10.14148/j.issn.1672-0482.2021.0619. 陈畅, 谢永艳, 黄丽萍. 荷叶碱药理作用的研究进展[J]. 南京中医药大学学报, 2021, 37( 4): 619- 624. DOI: 10.14148/j.issn.1672-0482.2021.0619.
[40]	QU YQ, ZHANG QY, TAN XY, et al. Effect of nuciferine against the proliferation of cholangiocarcinoma cells through Akt/mTOR/4EBP1-glycolytic pathway[J]. Nat Prod Res Dev, 2023, 35( 8): 1297- 1304, 1379. DOI: 10.16333/j.1001-6880.2023.8.002. 屈雅琴, 张倩玉, 谈相云, 等. 荷叶碱抑制Akt/mTOR/4EBP1-糖酵解通路抗胆管癌细胞增殖作用研究[J]. 天然产物研究与开发, 2023, 35( 8): 1297- 1304, 1379. DOI: 10.16333/j.1001-6880.2023.8.002.
[41]	DAI S, WANG C, ZHAO XT, et al. Cucurbitacin B: A review of its pharmacology, toxicity, and pharmacokinetics[J]. Pharmacol Res, 2023, 187: 106587. DOI: 10.1016/j.phrs.2022.106587.
[42]	LI L, DENG DJ, TAN XY, et al. Mechanism of cucurbitacin B in regulating glycolysis and inhibiting proliferation of HuCCT1 cells[J]. Chin J Exp Tradit Med Formulae, 2022, 28( 16): 74- 81. DOI: 10.13422/j.cnki.syfjx.20221624. 李励, 邓冬杰, 谈相云, 等. 葫芦素B调控糖酵解抑制HuCCT1细胞增殖的作用机制[J]. 中国实验方剂学杂志, 2022, 28( 16): 74- 81. DOI: 10.13422/j.cnki.syfjx.20221624.
[43]	LI YF, LIU YS, LI YS. Chemical composition and pharmacological effects of RadixBupleuri[J]. Northwest Pharm J, 2022, 37( 5): 186- 192. DOI: 10.3969/j.issn.1004-2407.2022.05.036. 李艳凤, 刘雅舒, 李艳生. 柴胡的化学成分与药理作用研究进展[J]. 西北药学杂志, 2022, 37( 5): 186- 192. DOI: 10.3969/j.issn.1004-2407.2022.05.036.
[44]	HE H, GUO JQ, HU YX, et al. Saikosaponin D reverses epinephrine- and norepinephrine-induced gemcitabine resistance in intrahepatic cholangiocarcinoma by downregulating ADRB2/glycolysis signaling[J]. Acta Biochim Biophys Sin, 2023: 55( 9): 1404- 1414. DOI: 10.3724/abbs.2023040.