Inhibition of PARP Potentiates Immune Checkpoint Therapy through miR-513/PD-L1 Pathway in Hepatocellular Carcinoma

PARP 抑制可通过 miR-513/PD-L1 通路增强肝细胞癌的免疫检查点治疗

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作者:Guoqiang Sun, Ganggang Miao, Zhitao Li, Wubin Zheng, Chunguang Zhou, Guangshun Sun, Hongyong Cao, Zhouxiao Li, Weiwei Tang

Background

The DNA repair enzyme poly(ADP-ribose) polymerase (PARP) is involved in DNA damage repair and cell death. However, the association between PARP's biological activities and the immune microenvironment in hepatocellular carcinoma (HCC) is unclear. The present study will explore whether combining a PARP inhibitor with anti-PD1 might improve the anti-HCC impact and explain how it works. Method: The PARP inhibitor olaparib was screened out of 867 drugs through Cell Counting Kit 8 (CCK-8) assay. The expression of PARP was verified through the TCGA and TISIDB databases. The impacts exerted by PARP inhibitor olaparib to HCC cells were assessed via wound healing, Transwell, and proliferation assay. In vivo, experiments were performed in a C57BL/6 mouse model to evaluate the function of PARP inhibitor olaparib combination with anti-PD1 in HCC and mice tumors were further detected by immunohistochemically staining. Result: Olaparib was selected as the research object on the basis of drug screening. The

Conclusion

The present study reveals that inhibition of PARP potentiates immune checkpoint therapy through the miR-513/PD-L1 pathway in HCC and the combination of PARP inhibitor olaparib and anti-PD1 is beneficial to HCC therapy.

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