Galectin-1-induced autophagy facilitates chemoresistance of hepatocellular carcinoma

• Main Authors: Yu-ChiSu, 蘇育琦
• Other Authors: Chih-Peng Chang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/33747281688676000867

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 101 === Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the priority treatment for HCC patients, drug resistance often leads to clinical failure. The mechanisms of such chemoresistance in HCC remain to be clarified. Previous studies showed that tumor microenvironment and autophagy may contribute to chemoresistance in many cancers. However, the number of identified autophagy-inducers within tumor microenvironment is still limited. Galectin-1 (Gal-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. The role of Gal-1 in chemoresistance of HCC is still unclear. In this study, we demonstrated that free-form Gal-1 triggers an autophagic flux to attenuate chemo-drugs-induced haptoma cell death. We showed that chemo-drugs, 5-fluorouracil and cisplatin, can stimulate hepatoma cells undergoing both apoptosis and autophagy. Pretreatment of free form Gal-1 can enhance chemo-drugs-induced autophagic flux through inhibiting AKT-mTOR activities and hence reduce cell death. The free form Gal-1-contributed chemoresistance in HCC requires its beta-galactoside binding activity, but is independent with intrinsic Gal-1 involvement. Autophagy-deficient cells fail to provide the free form Gal-1-induced chemoresistance, indicating that Gal-1-triggered autophagy is crucial for the resistance. Moreover, we found that autophagy deficient cells are not able to remove chemo-drugs-induced damaged mitochondria and lead to an increase in mitochondrial membrane potential (MMP) loss. However, Gal-1-triggered autophagy can target these damaged mitochondria to reduce MMP. In conclusion, we found that Gal-1 which is overexpressed in tumor microenvironment can contribute to chemoresistance by inducing autophagic flux and further eliminate chemo-drugs-induced damaged mitochondria. Our study revealed Gal-1 as a new therapeutic target for HCC treatment.