| Summary: | 碩士 === 國立嘉義大學 === 生化科技學系研究所 === 100 === Lung cancer is the most frequently diagnosed cancer with the leading cause of cancer mortality in the world. Curcumin (diferuloylmethane) is an active component of the Curcuma longa (turmeric), has been found anti-proliferative effect in multiple cancers. Mitomycin C (MMC), an alkylating antitumor agent in human lung cancer chemotherapy, leading to cytotoxicity and cell death through DNA cross-linking and breaking. Cisplatin (cis-diamminedichloroplatinum) is one of the most potent anticancer agents, displaying significant clinical activity against a variety of solid tumors, including lung cancers. The mechanisms of cisplatin resistance have been proposed, including enhancement of DNA repair and intracellular antioxidant activity, which block the induction of apoptosis. In all eukaryotes, Rad51 is a key enzyme of homologous-recombination. High level of Rad51 expression is resistant to cytotoxic agents. Excision repair cross-complementary 1 (ERCC1) is a protein involved the process of nucleotide excision repair. The ERCC1 gene is expressed at high levels in cancers and has been associated with resistance to platinum-based chemotherapy. Thymidine phosphorylase (TP) is a key protein in the pyrimidine nucleoside salvage pathway, and upregulation of it expression promotes tumor growth. In this study, we investigated the effect of curcumin enhancing the cisplatin or MMC-induced cytotoxicity in non-small cell lung cancer (NSCLC). Exposure human NSCLC cell line H1975 to MMC or cisplatin could increase protein levels of phosphorylated MKK1/2-ERK1/2. We also observed that the combined treatment of curcumin and these two chemotherapy drugs induced synergistic reduction protein levels of Rad51, ERCC1 and TP through MKK1/2-ERK1/2 inactivation pathway. Using individual small interfering RNA transfection to depletion of Rad51, ERCC1 and TP expression increased MMC or cisplatin-induced cytotoxic effect. Accordingly, we conclude that suppression of Rad51, ERCC1 and TP expression or co-treatment MMC, cisplatin with curcumin may be considered as potential therapeutic modalities for lung cancer.
|
|---|
