雷公藤内酯醇对小鼠H22腹水瘤细胞凋亡及PD-L1表达的影响
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摘要
目的探讨雷公藤内酯醇诱导H22腹水瘤细胞凋亡以及作用机制。方法采用腹腔注射肝癌H22细胞建立小鼠腹水瘤模型,80只成模小鼠随机分为对照组、雷公藤内酯醇低、中、高剂量(0.05, 0.1, 0.2 mg/kg)组,每组20只。观察小鼠体质量变化、生存期;计量腹水体积及计数腹水内肿瘤细胞数;流式细胞仪检测肿瘤细胞凋亡及程序性死亡受体-配体1(PD-L1)表达的变化。结果与对照组比较,雷公藤内酯醇3个剂量组小鼠的体质量增长缓慢,生存期中位数均有显著延长(P<0.01);雷公藤内酯醇低、中、高3个剂量组的腹水体积以及每毫升中的肿瘤细胞数均显著低于对照组(P<0.05);流式细胞术检测结果显示,不同剂量的雷公藤内酯醇可以显著诱导H22细胞凋亡并下调H22细胞PD-L1的表达(P<0.05,P<0.01)。结论雷公藤内酯醇可能通过诱导肝癌H22细胞凋亡及抑制PD-L1表达,发挥抗肝肿瘤的作用。
Objective To investigate the effects of Triptolide on apoptosis and PD-L1 expression in H22 hepatic ascitic tumor cells in mice. Method Eighty mice were injected intraperitoneally with H22 cells and divided into 4 groups: control group, low-dose TPL group( 0.05 mg/kg), medium-dose TPL group( 0.1 mg/kg) and high-dose TPL group(0.2 mg/kg). The weight change and survival period of mice were observed; the volume of ascites and the number of tumor cells were counted, and the apoptosis and PD-L1 expression on H22 cells were detected by flow cytometry. Result The TPL groups showed slower body weight increase and longer median survival time than the control group. The volume of ascites and the number of tumor cells decreased compared with the control group. In addition, TPL significantly induced H22 cell apoptosis and down-regulated PD-L1 expression in a dose-manner. Conclusion TPL may play an anti-hepatocellular carcinoma action by inducing H22 cell apoptosis and inhibiting the expression of programmed death receptor ligand 1.
Objective To investigate the effects of Triptolide on apoptosis and PD-L1 expression in H22 hepatic ascitic tumor cells in mice. Method Eighty mice were injected intraperitoneally with H22 cells and divided into 4 groups: control group, low-dose TPL group( 0.05 mg/kg), medium-dose TPL group( 0.1 mg/kg) and high-dose TPL group(0.2 mg/kg). The weight change and survival period of mice were observed; the volume of ascites and the number of tumor cells were counted, and the apoptosis and PD-L1 expression on H22 cells were detected by flow cytometry. Result The TPL groups showed slower body weight increase and longer median survival time than the control group. The volume of ascites and the number of tumor cells decreased compared with the control group. In addition, TPL significantly induced H22 cell apoptosis and down-regulated PD-L1 expression in a dose-manner. Conclusion TPL may play an anti-hepatocellular carcinoma action by inducing H22 cell apoptosis and inhibiting the expression of programmed death receptor ligand 1.
引文
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[15] Zhao X, Zhang Q, Chen L. Triptolide induces the cell apoptosis of osteosarcoma cells through the TRAIL pathway[J]. Oncol Rep,2016,36(3):1499-1505.
[16] 蒋涛,付立业,李妍. RNAi沉默肺腺癌A549细胞系PD-L1基因表达对其增殖和凋亡的影响[J]. 现代肿瘤医学,2015,23(2):177-180.
[17] 李义,王晶,克晓燕. PD-L1在淋巴瘤中的表达及其对淋巴瘤增殖和化疗抵抗的初步研究[J]. 中国实验血液学杂志, 2013,21(2):366-370.
[2] Lee H G, Park W J, Shin S J, et al. Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells[J]. Oncol Lett,2017,13(4):2817-2822.
[3] Zhao C P, Xu Z J, Guo Q, et al. Overexpression of suppressor of IKBKE 1 is associated with vincristine resistance in colon cancer cells[J]. Biomed Rep, 2016,5(5):585-588.
[4] Tanaka T, Kutomi G, Kajiwara T, et al. Cancer-associated oxidoreductase ERO1-alpha promotes immune escape through up-regulation of PD-L1 in human breast cancer[J]. Oncotarget, 2017,8(15):24706-24718.
[5] Van Der Kraak L, Goel G, Ramanan K, et al. 5-fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers[J]. J Immunother Cancer,2016,65(4):1-8.
[6] Zhang P, Su D M, Liang M, et al. Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis[J]. Mol Immunol,2008,45(5):1470-1476.
[7] Kupchan S M, Court W A, Dailey R G, et al. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii[J]. J Am Chem Soc,1972,94(20):7194-7195.
[8] 甘陈灵,邹玉莲,黄秀旺,等. 雷公藤内脂醇对肝癌H22细胞增殖凋亡及COX-2表达的影响[J]. 福建医科大学学报, 2017,51(3),146-149.
[9] 张鹏宇,张瑞,王雅贤. 雷公藤内脂醇抗肿瘤分子机制研究进展[J]. 中医药学报,2009,37(3):79-82.
[10] Liu M, Yeh J, Huang Y, et al. Effect of triptolide on proliferation and apoptosis of angiotensin Ⅱ-induced cardiac fibroblasts in vitro: a preliminary study[J]. Afr J Tradit Complement Altern Med, 2017,14(1):145-154.
[11] Yang L L, Wang X Y, Zheng L Y, et al. The role of FOXO3a-Bim signaling in triptolide induced bladder cancer T24 cells apoptosis[J]. Zhonghua Yi Xue Za Zhi,2017,97(15):1187-1190.
[12] Chen Y, Zhang J, Li J, et al. Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription[J]. Mol Immunol, 2006,43(8):1088-1098.
[13] Liang M, Fu J. Triptolide inhibits interferon-gamma-induced programmed death-1-ligand 1 surface expression in breast cancer cells[J]. Cancer Lett,2008,270(2):337-341.
[14] Sun Y Y, Xiao L, Wang D, et al. Triptolide inhibits viability and induces apoptosis in liver cancer cells through activation of the tumor suppressor gene p53[J]. Int J Oncol,2017,50(3):847-852.
[15] Zhao X, Zhang Q, Chen L. Triptolide induces the cell apoptosis of osteosarcoma cells through the TRAIL pathway[J]. Oncol Rep,2016,36(3):1499-1505.
[16] 蒋涛,付立业,李妍. RNAi沉默肺腺癌A549细胞系PD-L1基因表达对其增殖和凋亡的影响[J]. 现代肿瘤医学,2015,23(2):177-180.
[17] 李义,王晶,克晓燕. PD-L1在淋巴瘤中的表达及其对淋巴瘤增殖和化疗抵抗的初步研究[J]. 中国实验血液学杂志, 2013,21(2):366-370.