Inhibitory effect of iAPA- DC /CTL on HepG2 xenograft in nude mice
-
摘要:
目的观察经沉默免疫负调控基因(iAPA)技术处理的树突状细胞(DC)联同细胞毒性T淋巴细胞(CTL)(iAPA-DC/CTL)对HepG2细胞移植瘤的抑制作用。方法利用人肝癌细胞系HepG2建立裸鼠皮下移植瘤模型,将12只裸鼠随机分为2组:生理盐水对照组(C组)和iAPA-DC/CTL组(DC组),每组6只,行iAPA-DC/CTL治疗4次(1周/次)后处死。实验期间观察各组裸鼠的肿瘤生长,测量肿瘤长短径并描绘肿瘤生长曲线,称量瘤重并计算抑瘤率,病理检测。两组间均数比较采用成组t检验。结果造模成功率为92.31%。C组和DC组肿瘤体积分别为:(697.69±143.99)、(485.64±188.75)mm3,DC组生长相对缓慢(t=2.28,P<0.05);C组和DC组肿瘤重量分别为:(0.32±0.07)、(0.22±0.08)g,DC组肿瘤重量小于对照组(t=2.31,P<0.05),抑瘤率为30.39%。肿瘤免疫组化染色后T淋巴细胞计数分别为:C组未见、DC组(39.74±5.11)个/高倍视野,DC组肿瘤内T细胞数多于对照组(t=19.05,P<0.05)。...
-
关键词:
- 肝肿瘤,实验性 /
- 基因表达调控 /
- 树突细胞 /
- T淋巴细胞,细胞毒性
Abstract:Objective To investigate the inhibitory effect of inhibition of antigen presentation attenuators ( iAPA) - based dendritic cells ( DC) and cytotoxic T lymphocytes ( CTL) ( iAPA- DC/CTL) on HepG2 xenograft in nude mice. Methods Human hepatocarcinoma HepG2 cells were subcutaneously implanted into nude mice on nude mice to establish a HepG2 xenograft model transplanted tumor model of human HCC. Twelve nude mice were randomly and equally divided into two groups: normal saline control group ( C group) and iAPA- DC /CTL group ( DC group) . After four times of treatment with iAPA- DC /CTL ( once a week) , all mice were sacrificed. Tumor growth was evaluated by measuring the long and short diameters and delineating the tumor growth curve. The tumors were weighed, and the tumor inhibition rate was calculated. In addition, histopathological examination was performed. Comparison of means between the two groups was made by independent- samples t test. Results The HepG2 xenograft model was successfully established in 92. 31% of all mice. The tumor volume was 697. 69 ± 143. 99 mm3 in C group and 485. 64 ± 188. 75 mm3 in DC group; the tumor growth was significantly slower in DC group than in C group ( t = 2. 28, P < 0. 05) . The tumor weight was 0. 32 ± 0. 07 g in C group and 0. 22 ± 0. 08 g in DC group; DC group had a significantly lower tumor weight than C group ( t = 2. 31, P < 0. 05) , and the tumor inhibition rate was 30. 39%. After immunohistochemical staining, T lymphocyte count was 0 cell /high- power field ( HPF) in C group and 39. 74 ± 5. 11 cells /HPF in DC group; the number of T lymphocytes in DC group was significantly higher than that in C group ( t = 19. 05, P < 0. 05) . Conclusion iAPA- DC /CTL can effectively inhibit the growth of subcutaneous HepG2 xenograft in nude mice.
-
[1]LI Y, CHENG P.Advances in treatment of advanced hepatocellular cancer[J].J Clin Hepatol, 2014, 30 (3) :233-236. (in Chinese) 李焱, 程朋.中晚期肝癌临床治疗进展[J].临床肝胆病杂志, 2014, 30 (3) :233-236. [2]SHEN L, EVEL-KABLER K, STRUBE R, et al.Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity[J].Nat Biotechnol, 2004, 22 (12) :1546-1553. [3]HONG B, REN W, SONG XT, et al.Human suppressor of cytokine signaling 1 controls immunostimulatory activity of monocytederived dendritic cells[J].Cancer Res, 2009, 69 (20) :8076-8084. [4]UDAGAWA M, KUDO-SAITO C, HASEGAWA G, et al.Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination withcryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation[J].Clin Cancer Res, 2006, 12 (24) :7465-7475. [5]LIU YL, QIAN HX, ZHANG T, et al.Inhibitory effect of chemokine receptor-6-small interfering RNA on human HCCLM6 cell line subcutaneously implanted tumor in nude mice[J].Chin J Exp Surg, 2013, 30 (12) :2577-2579. (in Chinese) 刘业六, 钱海鑫, 张逖, 等.趋化因子受体-6小干扰RNA对人肝癌HCCLM6细胞裸鼠皮下移植瘤的抑制作用[J].中华实验外科杂志, 2013, 30 (12) :2577-2579. [6]LIN XF, WU JM, LIN CJ, et al.Effects of HBV S-ecdCD40L fusion gene modification on function of dendritic cells[J].J Med Res, 2013, 42 (12) :49-53. (in Chinese) 林贤凡, 吴金明, 林春景, 等.HBV S-ecdCD40L融合基因修饰对树突状细胞功能的影响[J].医学研究杂志, 2013, 42 (12) :49-53. [7]CHENG TT, XU X, GE HP, et al.Cytotoxicity effect of lentivirus-mediated suicide genes on dendritic cells[J].J Med Res, 2014, 43 (4) :71-75. (in Chinese) 程婷婷, 徐希, 葛杭萍, 等.慢病毒介导的自杀基因对树突状细胞的杀伤作用[J].医学研究杂志, 2014, 43 (4) :71-75. [8]CURIEL TJ, COUKOS G, ZOU L, et al.Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival[J].Nat Med, 2004, 10 (9) :942-949. [9]PALUCKAL AK, UENO H, FAY J, et al.Dendritic cells:a critical player in cancer therapy?[J].J Immunother, 2008, 31 (9) :793-805. [10]PARK HY, JIN JO, SONG MG, et al.Expression of dendritic cell markers on cultured neutrophils and its modulation by anti-apoptotic and pro-apoptotic compounds[J].Exp Mol Med, 2007, 39 (4) :439-449. [11]TATSUMI T, TAKEHARA T, YAMAGUCHI S, et al.Intrahepatic delivery of alpha-galactosylceramide-pulsed dendritic cells suppresses liver tumor[J].Hepatology, 2007, 45 (1) :22-30. [12]PALMER DH, MIDGLEY RS, MIRZA N, et al.A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma[J].Hepatology, 2009, 49 (1) :124-132.引证本文:FU HF, ZHOU WB, DING YM, et al.Inhibitory effect of iAPA-DC/CTL on HepG2 xenograft in nude mice[J].J Clin Hepatol, 2014, 30 (9) :891-894. (in Chinese) 付海峰, 周文波, 丁佑铭, 等.经沉默免疫负调控基因技术处理的树突状细胞联同细胞毒性T淋巴细胞对HepG2细胞移植瘤的抑制作用[J].临床肝胆病杂志, 2014, 30 (9) :891-894. -

计量
- 文章访问数: 2948
- HTML全文浏览量: 21
- PDF下载量: 582
- 被引次数: 0