肝癌组织中PD-L1和HIF-1α的相关性研究
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摘要
目的:探讨细胞程序化死亡-配体1(PD-L1)和缺氧诱导因子-1α(HIF-1α)在肝癌组织中的相关性,研究缺氧信号通路阻断剂YC-1对肝癌细胞中的PD-L1表达的影响。方法:采用免疫组化染色法检测90例肝癌组织中PD-L1和HIF-1α的表达,分析两者之间的相关性。将肝癌细胞Huh7和Hep3B细胞分别置于乏氧培养箱中,对照组加入DMSO,实验组加入50μmol/L的YC-1,作用48 h后分别提取总RNA和蛋白。用Real-time PCR和Western blot分别检测两组细胞中PD-L1的表达水平。结果:PD-L1和HIF-1α的表达在肝癌组织中呈正相关,阻断缺氧信号通路后PD-L1的表达下调。结论:HIF-1α信号通路激活是导致肝癌组织中PD-L1表达升高的原因之一,加以阻断可以抑制PD-L1的表达。
Objective: To investigate the correlation between PD-L1 and HIF-1α in hepatocel ular carcinoma(HCC), and to investigate the effect of hypoxia signal pathway blocker YC-1 on PD-L1 expression in hepatocarcinoma cel s. Methods: The expression of PD-L1 and HIF-1α in 90 cases of HCC was detected by immunohistochemical staining, and the correlation between them was analyzed.Huh7 and Hep3 B cel s were incubated in the hypoxic incubator. The control group was treated with DMSO, while 50 μmol/L YC-1 was added to the experimental group. The m RNA and protein were extracted after 48 h. The expression of PD-L1 was detected by Real-time PCR and Western Blot analysis.Results: PD-L1 and HIF-1α were positively correlated in HCC tissues, and the expression of PD-L1 was down-regulated after blocking the hypoxia signaling pathway. Conclusions: HIF-1α pathway activation is one of the reasons leading to the increase of PD-L1 expression in hepatocel ular carcinoma tissues, and block the hypoxia signaling pathway can inhibit the expression of PD-L1.
Objective: To investigate the correlation between PD-L1 and HIF-1α in hepatocel ular carcinoma(HCC), and to investigate the effect of hypoxia signal pathway blocker YC-1 on PD-L1 expression in hepatocarcinoma cel s. Methods: The expression of PD-L1 and HIF-1α in 90 cases of HCC was detected by immunohistochemical staining, and the correlation between them was analyzed.Huh7 and Hep3 B cel s were incubated in the hypoxic incubator. The control group was treated with DMSO, while 50 μmol/L YC-1 was added to the experimental group. The m RNA and protein were extracted after 48 h. The expression of PD-L1 was detected by Real-time PCR and Western Blot analysis.Results: PD-L1 and HIF-1α were positively correlated in HCC tissues, and the expression of PD-L1 was down-regulated after blocking the hypoxia signaling pathway. Conclusions: HIF-1α pathway activation is one of the reasons leading to the increase of PD-L1 expression in hepatocel ular carcinoma tissues, and block the hypoxia signaling pathway can inhibit the expression of PD-L1.
引文
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[9] Zhang L, Qiu M, Jin Y, et al. Programmed cell death ligand 1(PD-L1)expression on gastric cancer and its relationship with clinico-pathologic factors[J]. Int J Clin Exp Patho, 2015, 8(9):11084-11091.
[10]闫智永,唐桥斐,李赛楠,等. PD1/PDL1信号途径在小鼠变应性鼻炎发病中的作用[J].山东医药,2017,57(12):23-26.
[11]鹿玉印,郭秀丽.靶向抑制PD-L1/PD-1的免疫治疗恶性黑色素瘤新进展[J].中国药学杂志,2015,50(22):1931-1935.
[12] Liu H, Shen J, Lu K. IL-6 and PD-L1 blockade combination in-hibits hepatocellular carcinoma cancer development in mousemodel[J]. Biochem Biophys Res Commun, 2017, 486(2):239-244.
[13]黄志煜,李晖,范云.抗PD-1/PD-L1单抗治疗肺癌临床研究进展[J].中国肺癌杂志,2015(11):706-713.
[14] Dai X, Xue J, Hu J, et al. Positive expression of programmed deathligand 1 in peritumoral liver tissue is associated with poor survivalafter curative resection of hepatocellular carcinoma[J]. Transl On-col, 2017, 10(4):511-517.
[2]张新伟,任秀宝. PD-1抑制性抗体治疗肿瘤的临床研究现状[J].医学与哲学(B),2015,36(2):22-24.
[3] Jung HI, Jeong D, Ji S, et al. Overexpression of PD-L1 and PD-L2is associated with poor prognosis in patients with hepatocellular car-cinoma[J]. Cancer Res Treat, 2016, 49(1):246-254.
[4]刘利平,杨盛力,何婉,等.乙肝病毒X蛋白上调肝癌细胞缺氧诱导因子-1α的作用和机制研究[J].中国癌症杂志,2015,25(5):333-338.
[5] Liu LP, Ho RL, Chen GG, et al. Sorafenib inhibits hypoxia-in-ducible factor-1αsynthesis:implications for antiangiogenic activityin hepatocellular carcinoma[J]. Clin Cancer Res, 2012, 18(20):5662-5671.
[6] Zhang Y, Kang S, Shen J, et al. Prognostic significance of pro-grammed cell death 1(PD-1)or PD-1 ligand 1(PD-L1)expressionin epithelial-originated cancer:a meta-analysis[J]. Medicine, 2015,94(6):e515.
[7] Ono Y, Perez-Gutierrez A, Nakao T, et al. Graft-infiltrating PD-L1(hi)cross-dressed dendritic cells regulate anti-donor T cell re-sponses in mouse liver transplant tolerance[J]. Hepatology, 2017,101:S30-S31.
[8] Zhou ZJ, Zhan P, Song Y. PD-L1 over-expression and survival inpatients with non-small cell lung cancer:a meta-analysis[J]. TranslLung Cancer Res, 2015, 4(2):203-208.
[9] Zhang L, Qiu M, Jin Y, et al. Programmed cell death ligand 1(PD-L1)expression on gastric cancer and its relationship with clinico-pathologic factors[J]. Int J Clin Exp Patho, 2015, 8(9):11084-11091.
[10]闫智永,唐桥斐,李赛楠,等. PD1/PDL1信号途径在小鼠变应性鼻炎发病中的作用[J].山东医药,2017,57(12):23-26.
[11]鹿玉印,郭秀丽.靶向抑制PD-L1/PD-1的免疫治疗恶性黑色素瘤新进展[J].中国药学杂志,2015,50(22):1931-1935.
[12] Liu H, Shen J, Lu K. IL-6 and PD-L1 blockade combination in-hibits hepatocellular carcinoma cancer development in mousemodel[J]. Biochem Biophys Res Commun, 2017, 486(2):239-244.
[13]黄志煜,李晖,范云.抗PD-1/PD-L1单抗治疗肺癌临床研究进展[J].中国肺癌杂志,2015(11):706-713.
[14] Dai X, Xue J, Hu J, et al. Positive expression of programmed deathligand 1 in peritumoral liver tissue is associated with poor survivalafter curative resection of hepatocellular carcinoma[J]. Transl On-col, 2017, 10(4):511-517.