Cisplatin与 DNA 交联引起癌细胞中 DNA 损伤，可用于抗肿瘤化疗药物方向的研究。

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文章：PD-1/PD-L1 enhanced cisplatin resistance in gastric cancer through PI3K/AKT mediated P-gp expression

作者：Lijun Wu 1, Shiyi Cai 1, Yiyun Deng 1, Zhe Zhang 1, Xiehai Zhou 2, Yong Su 3, Dujuan Xu 4

PMID: 33581579    DOI: 10.1016/j.intimp.2021.107443

Background: 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.  

Methods: 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.  

Results: We found that the level of PD-1 was significantly increased in human gastric cancer tissues and drugresistant 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.  

Conclusion: PD-1/PD-L1 enhanced cisplatin resistance in gastric cancer through PI3K/AKT mediated P-gp  expression.