GSK-3β pathway is involved in amphiregulin-induced resistance to vincristine therapy in oral squamous cell carcinoma

• Main Authors: Wen-Ling Li, 李汶鈴
• Other Authors: Chen,Jui-Chieh
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/4p2q2r

碩士 === 國立嘉義大學 === 生化科技學系研究所 === 106 === At present, oral cancer is ranked the fifth most common cancer in Taiwan. Of these, oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral cancers. Despite advances in surgery, radiotherapy, and chemotherapy, the long-term survival rates with OSCC have not significantly improved. Vincristine (VCR), an alkaloid extracted from catharanthus roseus, can effectively affect the growth of rapidly dividing cells and has been widely used in the treatment of many cancers. Despite the treatment of VCR proven benefits for antitumor activity, there is often the development of resistance after a period of treatment leading to treatment failure. Therefore, new strategies should be developed to improve the therapeutic effect in OSCC patients. There are many mechanisms of drug resistance, including the reciprocal interplay among different types of cells within tumor microenvironment. Tumor cells can excessively secrete specific proteins, which may affect responses to drugs, resulting in resistance and decreased survival rate of patients. The aim of the present study was to identify which secreted proteins are involved in the VCR resistance and its effects on those pathways. Our results showed that amphiregulin (AREG) was highly secreted in VCR resistant cells. Pretreatment with exogenous recombinant AREG significantly rendered OSCC cells more resistant to VCR. In addition, knockdown and overexpression of AREG was also used to find that it does affect the sensitivity of OSCC cells to VCR. Finally, this study also found that amphiregulin may activate the glycogen synthase kinase 3 beta (GSK-3β) signaling pathway and promote OSCC cells resistance to VCR. These findings may help to develop new therapeutic drugs to improve the prognosis of OSCC patients in future.