PI3K/AKT/mTOR通路
顺铂
癌症研究
癌细胞
蛋白激酶B
癌症
免疫印迹
PD-L1
流式细胞术
MTT法
生物
化学
分子生物学
免疫系统
信号转导
细胞生长
下调和上调
免疫学
细胞生物学
免疫疗法
生物化学
化疗
基因
遗传学
作者
Lijun Wu,Shiyi Cai,Yiyun Deng,Zhe Zhang,Xie-Hai Zhou,Yong Su,Dujuan Xu
标识
DOI:10.1016/j.intimp.2021.107443
摘要
Programmed cell death receptor 1 (PD-1) is an immunosuppressive molecule expressed on T cells, and its ligand (PD-L1) which expressed on tumor cells play pivotal roles in regulating host immune responses. However, little is known whether PD-1/PD-L1 axis could directly activates intracellular oncogenic signaling pathways in tumor cells, leading to tumor resistance. In the present study, the expression of PD-1 and PD-L1 in the tissues of gastric cancer was detected by western blot and immunofluorescence. The effect of PD-L1-Fc and cisplatin on resistant gastric cancer cells was examined by MTT assay and Flow Cytometry. In addition. The effect of PD-L1-Fc on the expression of P-gp in gastric cancer cells and resistant gastric cancer cells was detected by quantitative real-time reverse-transcription PCR (qRT-PCR) and western blot. The molecular mechanisms of the regulation of cisplatin and PD-L1-Fc treatment were evaluated by western blot. We found that the level of PD-1 was significantly increased in human gastric cancer tissues and drug-resistant gastric cancer cells and P-gp was the same result. The PD-L1 could reduce the level of cell damage caused by cisplatin. In addition, we found PD-L1 can also up-regulate the expression of P-gp. Mechanistically, PD-L1 activated the PI3K/AKT signaling pathway in which PI3K/AKT pathway inhibition attenuated the upregulation of P-gp. PD-1/PD-L1 enhanced cisplatin resistance in gastric cancer through PI3K/AKT mediated P-gp expression.
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