自噬
吖啶橙
癌症研究
细胞凋亡
程序性细胞死亡
组织蛋白酶B
顺铂
组织蛋白酶D
肝细胞癌
癌细胞
活力测定
肝癌
生物
化学
癌症
化疗
医学
内科学
酶
生物化学
标识
DOI:10.1016/j.bbrc.2020.09.068
摘要
Hepatocellular carcinoma (HCC) is a common malignancy with high cancer-associated mortality. Suppressing autophagy has been reported to promote the efficiency of chemotherapy in HCC. Daurisoline (DAS) is a constituent of Rhizoma Menispermi, and functions as a potential autophagy inhibitor to perform different cellular events. In the present study, we found that DAS treatment up-regulated autophagosomes in HCC cells, accompanied with the increases of LC3-II and p62, demonstrating the disturbance of autophagic flux. Then, by the colocalization analysis, we identified that DAS did not repress the fusion of autophagosomes and lysosomes in HCC cells. However, Lysotracker and acridine orange (OA) staining showed that DAS could suppress lysosomal acidification, as evidenced by the decreased red fluorescence. Consistently, significant decreases in mature form of cathepsin B and cathepsin D were detected in DAS-treated HCC cells. Furthermore, DAS treatment markedly promoted the anti-cancer effects of cisplatin (cDDP) on HCC cells, as revealed by the dramatically reduced cell viability and proliferation, whereas the enhanced apoptosis. Moreover, the nude mice xenograft models with HCC confirmed that compared with cDDP alone group, DAS combined with cDDP significantly reduced tumor progression in vivo. Taken together, these findings elucidated that DAS could restrain autophagic flux, potentiating the chemosensitivity of HCC cells to cDDP treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI