title: Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.
authors: Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors: Yu-Chi
authors: YC
authors: Su
authors: The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors: Goutham Venkata Naga
authors: GV
authors: Davuluri
authors: Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors: Cheng-Hao
authors: CH
authors: Chen
authors: Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors: Dong-Che
authors: DC
authors: Shiau
authors: Department of Pathology, Chia-Yi Christian Hospital, Chiayi 600, Taiwan.|Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 701, Taiwan.
authors: Chien-Chin
authors: CC
authors: Chen
authors: Translational Research Center, Taipei Medical University, Taipei 110, Taiwan.
authors: Chia-Ling
authors: CL
authors: Chen
authors: Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.
authors: Yee-Shin
authors: YS
authors: Lin
authors: Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.
authors: Chih-Peng
authors: CP
authors: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D063306:Mitophagy / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D037483:Galectin 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin