Prodigiosin inhibits cholangiocarcinoma cell proliferation and induces apoptosis via suppressing SNAREs-dependent autophagy

Cancer Cell International

Shiyu Chen¹  Yazhu Deng²  Kun Cai³  Dijie Zheng³  Linhan Lei³  Chunchen Wu³  Chao Yu³  Chengyi Sun³ 

[1] Guizhou Medical University, 550004, Guiyang, China;School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China;Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China;Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, China;Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, Guiyang, China;Guizhou Medical University, 550004, Guiyang, China;School of Clinical Medicine, Guizhou Medical University, Guiyang, China;Department of General Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China;Guizhou Medical University, 550004, Guiyang, China;School of Clinical Medicine, Guizhou Medical University, Guiyang, China;Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China;Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, China;Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, Guiyang, China;

关键词: Prodigiosin;    SNAREs complex;    Cholangiocarcinoma;    Autophagy;    Proliferation;   

DOI  :  10.1186/s12935-021-02355-3

来源: Springer

【 摘 要 】

BackgroundProdigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eye-catching research point in recent years for its anticancer activity. However, the role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague.MethodsThe proliferation of CCA cells was detected by Cell Counting Kit-8(CCK-8), Colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was evaluated by flow cytometry assay and western blot assay. The effects of PG or SNAREs on cell autophagy were measured by autophagy flux assay and western blot assay. Xenograft mouse models were used to assess the role of PG in CCA cells in vivo.ResultsPG could inhibit the proliferation and viability of CCA cells in a concentration- and time-dependent manner via suppressing the late stage of autophagy. Mechanistically, PG inhibits the fusion of autophagosomes and lysosomes by blocking STX17 and SNAP29, components of soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs)complex. When STX17 and SNAP29 were overexpressed, the inhibitory effect of PG on CCA cells autophagy was relieved. In addition, PG showed obvious inhibitory effects on cancer cell viability but no toxic effects on organs in xenotransplantation models.ConclusionTaken together, our results demonstrated that PG inhibits CCA cell proliferation via suppressing SNAREs-dependent autophagy, implying that PG could be a potential chemotherapy drug for advanced CCA.

【 授权许可】

CC BY