2. Academic Validation
  3. (-)-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.
PMID: 35872041 DOI: 10.1016/j.cbi.2022.110060
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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