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Crosstalk between autophagy inhibitor and salidroside-induced apoptosis: A novel strategy for autophagy-based treatment of hepatocellular cancer  ( SCI-EXPANDED收录)   被引量:2

文献类型:期刊文献

英文题名:Crosstalk between autophagy inhibitor and salidroside-induced apoptosis: A novel strategy for autophagy-based treatment of hepatocellular cancer

作者:Jiang, Bing[1];Cui, Yangyang[1];Ma, Xinxin[2];Zhang, Yanmei[2];Feng, Xin[2];Yang, Tao[2];Feng, Longfei[2];Guo, Wenjing[2];Li, Yangyang[2];Wang, Tao[3];Guo, Huan[1,3];Li, Haining[3];Duan, Ying[4];Su, Haixiang[1,3,5]

第一作者:Jiang, Bing

通信作者:Su, HX[1]

机构:[1]Gansu Univ Tradit Chinese Med, Dept Integrated Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Dept Basic Med, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Prov Canc Hosp, Gansu Prov Acad Inst Med Res, Translat Med Res Ctr, Lanzhou 730050, Gansu, Peoples R China;[4]Gansu Prov Canc Hosp, Dept Ultrasound, Lanzhou 730050, Gansu, Peoples R China;[5]Gansu Prov Canc Hosp, Gansu Prov Acad Inst Med Res, Translat Med Res Ctr, 2 Xiaoxihu East St, Lanzhou 730050, Gansu, Peoples R China

第一机构:甘肃中医药大学中西医结合学院

通信机构:[1]corresponding author), Gansu Prov Canc Hosp, Gansu Prov Acad Inst Med Res, Translat Med Res Ctr, 2 Xiaoxihu East St, Lanzhou 730050, Gansu, Peoples R China.

年份:2023

卷号:124

外文期刊名:INTERNATIONAL IMMUNOPHARMACOLOGY

收录:;Scopus(收录号:2-s2.0-85174351795);WOS:【SCI-EXPANDED(收录号:WOS:001102065700001)】;

基金:This work was supported by the Key Talent Project of Gansu Province (Grant No. 2021RCXM057) , the Longyuan Youth Innovation and Entrepreneurship Talent Project in Gansu Province (Grant No. 2022LQGR76) , the Program of Technology Plan in Gansu Province (Grant No. 18JR2FA010) , the Research Project of Traditional Chinese Medicine in Gansu Province (Grant No. GZKP-2021-21) , the Lanzhou Science and Technology Plan Project (Grant No. 2021-1-90) and the Gansu Provincial Department of Education: "Double First-Class" Key Scientific Research Project (Grant No. GSSYLXM-08,-09) .

语种:英文

外文关键词:Salidroside; Liver cancer; Autophagy; Mitochondrial apoptosis; Crosstalk; PI3K/Akt/mTOR

摘要:Autophagy regulates many cell function related to cancer, including cell proliferation, invasion and apoptosis. Therefore, we investigated the potential value of crosstalk between autophagy and apoptosis. The present study demonstrated that seven autophagy related genes were screened from the biological network of salidroside (Sal) acting on liver cancer. The GO analysis showed that these genes were mainly involved in apoptosis and autophagy. The KEGG analysis showed that these genes regulated the process of liver cancer through Th17 cell differentiation, PI3K-Akt signaling pathway and other pathways. Moreover, seven genes were positively correlated with tumor purity, number of B cells, number of CD4(+) T cells, number of CD8(+) T cells, number of macrophages, number of dendritic cells and number of neutrophils. The overall survival time of liver cancer patients in the high expression group of BIRC5, HSP90AB1 and MTOR was lower than that in the low expression group (P < 0.05), while the overall survival time of the liver cancer patients in the high expression group of DLC1 and FOXO1 was higher than that in the low expression group (P < 0.05). In the pan-cancer analysis, we also found that BIRC5, HSP90AB1, MTOR, and ITGA6 were highly expressed in various cancers, while DLC1, FOXO1, and FOS were low expressed in various cancers. In the molecule docking analysis, we found that FOS, HSP90AB1, and MTOR had the best binding ability. Notably, in the vitro validation experiments, Sal was confirmed to induce autophagy and apoptosis, inhibite invasion and metastasis of liver cancer cells through the PI3K/Akt/mTOR signaling pathway. Meanwhile, inhibition of autophagy by chloroquine diphosphate (CQ) promoted Sal-induced mitochondrial apoptosis via corresponding cell and animal experiments. We speculated that Sal-induced autophagy might be a protective mechanism, inhibition of autophagy could further promote the progression of liver cancer. It may provide important insight into the molecular mechanism of crosstalk between autophagy and apoptosis, and provide a new theoretical basis of Sal combined with autophagy inhibitors as a adjuvant chemotherapeutic strategy for human liver cancer.

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