Investigating the molecular roles and mechanisms of Galectin-3 on drug resistance in colon cancer

• Main Authors: Yung-KuoLee, 李永國
• Other Authors: Chuan-Fa Chang
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/bed2eq

博士 === 國立成功大學 === 基礎醫學研究所 === 105 === Colorectal cancer (CRC) is among the top ten causes of cancer-related death worldwide, and it also accounts for the highest incidence of cancer in Taiwan over the past decade. The prognosis of CRC remains poor because of the high recurrence rates and low response to chemotherapy (drug resistance). Many studies have demonstrated two factors, namely the upregulation of multidrug resistance (MDR)-associated proteins and presence of tumor-initiating cells (cancer-initiating cells, CICs, or cancer stem cells, CSCs), that are correlated with a high rate of recurrence and high metastatic ability. CSCs are capable of self-renewal and differentiation into various types of cancer. Moreover, CSCs are proposed to be responsible for resistance to chemotherapy. Therefore, this study investigated the roles and molecular mechanisms of drug resistance in CRC, in addition to elucidating the drug resistance mechanisms in colon CSCs. We determined that galectin-3 (Gal-3) participated in drug resistance modulation in CRC and in maintaining stemness in CSCs. Increased Gal-3 expression in colon cancer cells involves the upregulation of MDR-related proteins through the induction of β-catenin/GSK-3β signaling. Furthermore, the expression of Gal-3 increased significantly in colon tumor spheres. The suppression of Gal-3 through RNA interference in colon cancer cells decreased Gal-3 expression and reduced the size, number, and stemness-related proteins in tumor spheres. In addition, these phenomena could be rescued by Gal-3 inhibitor treatment. Thus, the exposure of colon cancer cells to anticancer drug stimulation or plasticizing agents may promote the expression of multidrug-resistant proteins through different molecular mechanisms and exhibit CIC-related gene expression and activity. Taken together, Gal-3 plays key roles in MDR and tumor-initiating cell properties. Accordingly, we suggest that targeting galectin-3 may be a potent approach for improving colon cancer therapy.