肝细胞癌
基因敲除
细胞凋亡
化学
癌症研究
生物
分子生物学
生物化学
作者
Liyuan Hao,Yinglin Guo,Qing Peng,Zhiqin Zhang,Jingmin Ji,Yiwei Liu,Yu Xue,Caige Li,Kangning Zheng,Xinli Shi
出处
期刊:Phytomedicine
[Elsevier]
日期:2022-02-01
卷期号:96: 153913-153913
被引量:17
标识
DOI:10.1016/j.phymed.2021.153913
摘要
Anti-PD-1 was used to treat for many cancers, but the overall response rate of monoclonal antibodies blocking the inhibitory PD-1/PD-L1 was less than 20%. Lipid droplet (LD) deposition reduced chemotherapy efficacy, but whether LD deposition affects anti-PD-1 treatment and its mechanism remains unclear. Dihydroartemisinin (DHA) was FDA proved antimalarial medicine, but its working mechanism on LD deposition has not been clarified.This study aimed to elucidate the mechanism of DHA reducing LDs deposition and improving the efficacy of anti-PD-1.LD numbers and area were separately detected by electron microscopy and oil Red O staining. The expression of YAP1 and PLIN2 was detected by immunohistochemical staining in liver cancer tissues. Transcription and protein expression levels of YAP1 and PLIN2 in cells were detected by qRT-PCR and Western blot after DHA treated HepG2215 cells and Yap1LKO mice.LD accumulation was found in the liver tumor cells of DEN/TOPBCOP-induced liver tumor mice with anti-PD-1 treatment. But DHA treatment or YAP1 knockdown reduced LD deposition and PLIN2 expression in HepG2215 cells. Furthermore, DHA reduced the LD deposition, PLIN2 expression and triglycerides (TG) content in the liver tumor cells of Yap1LKO mice with liver tumor.Anti-PD-1 promoted LD deposition, while YAP1 knockdown/out reduced LD deposition in HCC. DHA reduced LD deposition by inhibiting YAP1, enhancing the effect of anti-PD-1 therapy.
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