1. Academic Validation
  2. (-)-Gossypol enhances the anticancer activity of epirubicin via downregulating survivin in hepatocellular carcinoma

(-)-Gossypol enhances the anticancer activity of epirubicin via downregulating survivin in hepatocellular carcinoma

  • Chem Biol Interact. 2022 Sep 1;364:110060. doi: 10.1016/j.cbi.2022.110060.
Wenbin Jiang 1 Wan Wang 2 Liangbo Sun 3 Yunhua Xiao 4 Teng Ma 2 Bosheng Li 1 Xiaojing Yan 1 Yaran Wu 3 Hongli Li 5 Jiqin Lian 6 Fengtian He 7
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
  • 2 Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China.
  • 3 Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
  • 4 Department of Nuclear Medicine, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
  • 5 Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
  • 6 Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China. Electronic address: lianjiqin@sina.com.
  • 7 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, China. Electronic address: hefengtian66@163.com.
Abstract

Epirubicin (EPI)-based transarterial chemoembolization is an effective therapy for advanced hepatocellular carcinoma (HCC). However, EPI-induced Survivin expression limits its tumor-killing potential in HCC. Interestingly, (-)-gossypol ((-)-Gsp), a male contraceptive, suppresses various malignancies. More importantly, (-)-Gsp also holds promise for enhancing the antitumor effects of chemotherapy in numerous Cancer types. In the present study, we demonstrated for the first time that (-)-Gsp-sensitized EPI inhibited cell growth and induced Apoptosis of HCC cells in vitro. Furthermore, (-)-Gsp sensitized EPI by attenuating the EPI-elevated Survivin protein levels. Mechanistic studies showed that EPI stimulated Survivin protein synthesis by promoting translation initiation, which was alleviated by (-)-Gsp mainly through suppressing the AKT-4EBP1/p70S6K-survivin and ERK-4EBP1-survivin pathways. HCC xenograft experiments in nude mice also showed that (-)-Gsp treatment acted synergistically with EPI to repress xenograft tumor growth. Overall, our proof-of-concept results may pave the way for novel strategies for the treatment of HCC based on the combination of EPI and (-)-Gsp.

Keywords

(−)-Gossypol; Epirubicin; Hepatocellular carcinoma; Sensitization; Survivin.

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