自噬
PI3K/AKT/mTOR通路
蛋白激酶B
癌症研究
细胞凋亡
癌细胞
细胞生长
生物
细胞培养
激酶
癌症
细胞生物学
化学
生物化学
遗传学
作者
Zhongwei Xu,Jun Bao,Xiaohan Jin,Heng Li,Kaiyuan Fan,Zhidong Wu,Ming Yao,Yan Zhang,Gang Liu,Dan Wang,Xiaoping Yu,Jia Guo,Rui‐Cheng Xu,Qian Gong,Fengmei Wang,Jin Wang
标识
DOI:10.1142/s0192415x23500726
摘要
Cinobufagin, a cardiotonic steroid derived from toad venom extracts, exhibits significant anticancer properties by inhibiting Na[Formula: see text]/K[Formula: see text]-ATPase in cancer cells. It is frequently used in clinical settings to treat advanced-stage cancer patients, improving their quality of life and survival time. However, its long-term use can result in multidrug resistance to other chemotherapy drugs, and the exact mechanism underlying this effect remains unknown. Therefore, this study explores the molecular mechanism underlying the anticancer effects of cinobufagin in hepatocellular carcinomas (HCCs), specifically in HepG2 and Huh-7 cells. As determined using transcriptome analysis, cinobufagin-triggered protective autophagy suppressed cell apoptosis in liver cancer HepG2 and Huh-7 cells by inhibiting the phosphoinositide-3-Kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway. Cinobufagin-inhibited cell proliferation, induced apoptosis, and generated cell autophagy by upregulating the expression of MAP1 light chain 3 protein II, Beclin1, and autophagy-related protein 12–5. In addition, the autophagy inhibitor MRT68921 improved the antiproliferative and proapoptotic effects of cinobufagin in the studied cell lines. Overall, this study suggests that combining cinobufagin with an autophagy inhibitor can effectively treat HCC, providing a potential strategy for cancer therapy.
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