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Cisplatin promotes the expression level of PD-L1 in the microenvironment of hepatocellular carcinoma through YAP1.
Molecular and Cellular Biochemistry ( IF 4.3 ) Pub Date : 2020-08-06 , DOI: 10.1007/s11010-020-03861-0
Shenghao Li 1, 2 , Jingmin Ji 1 , Zhiqin Zhang 1 , Qing Peng 1 , Liyuan Hao 1 , Yinglin Guo 1 , Wenhan Zhou 1 , Qingzhuo Cui 1 , Xinli Shi 1, 2
Affiliation  

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. However, the immune tolerance limits the effect of chemotherapeutic drugs. Therefore, the mechanism of cisplatin in promoting PD-L1 expression by YAP1 was investigated in the present study, and we found that cisplatin increased the expression level of YAP1 in the mouse liver with H22 cells. Meanwhile, cisplatin improved the expression level of PD-L1, IL-1β and CCL2 in the tumor microenvironment. Further, cisplatin also enhanced the expression level of YAP1 in shYAP1 HepG2215 cells. The expression of PD-L1 was decreased by Verteporfin, YAP1 inhibitor, during the treatment of DEN/TCPOBOP-induced liver cancer in C57BL/6 mice. These results suggested that cisplatin could deteriorate the immunosuppressive microenvironment through increasing PD-L1, CCL2, IL-1β by upregulated YAP1 expression. Therefore, the study suggested that YAP1 blockade destroyed the immunosuppressive microenvironment of cancer to improve the effect of chemotherapy in HCC.



中文翻译:

顺铂通过YAP1促进肝细胞癌微环境中PD-L1的表达水平。

肝细胞癌(HCC)是全球最致命的恶性肿瘤之一。但是,免疫耐受性限制了化学治疗药物的作用。因此,本研究探讨了顺铂促进YAP1表达PD-L1的机制,我们发现顺铂增加了H22细胞在小鼠肝脏中YAP1的表达水平。同时,顺铂提高了PD-L1,IL-1β和CCL2在肿瘤微环境中的表达水平。此外,顺铂还增强了shYAP1中YAP1的表达水平。HepG2215细胞。在DEN / TCPOBOP诱导的C57BL / 6小鼠肝癌治疗中,Yert抑制剂Verteporfin降低了PD-L1的表达。这些结果表明,顺铂可能通过上调YAP1表达来增加PD-L1,CCL2,IL-1β,从而破坏免疫抑制微环境。因此,该研究表明,YAP1阻断可破坏癌症的免疫抑制微环境,从而改善HCC化疗的效果。

更新日期:2020-08-06
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