| Summary: | 碩士 === 中山醫學大學 === 醫學分子毒理學研究所 === 97 === Lung cancer is a seriously cause of cancer deaths in the worldwide, and that is a disease of uncontrolled cell growth in tissues of the lung. The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Despite recent advances in the treatment, lung cancer remains an incurable disease. This calls for an effort to develop novel therapeutics in order to increase survival of patients and decrease the tocixity of drug. Here, we evaluated the potential antitumor effect of Pemetrexed (a NSCLC chemotherapy drug) with supplementated vitamin B12 or folic acid to treat the cells. We found that NSCLC cell lines have different sensitivity for Pemetrexed treatment in various serum concentration. Pemetrexed was more resistant to the cells in 10% serum. Furthermore, we also demonstrated that cells growth inhibition of Pemetrexed treatmented cells can be increased through vitamin supplementation (folic acid and vitamin B12) with three NSCLC cell lines tested. Under 2% serum conditions, the sensitization ability by vitamin B12 and folic acid supplementation was not observed. Our data also showed that induction of apoptosis by Pemetrexed treatment can be increased with vitamin B12 or/and folic acid supplementation. The sensitization effect is specific for Pemetrexed, since there is no other chemotherapy drug efficacy can be inproved by addition of vitamin B12 or folic acid. However, Pemetrexed can induce apoptosis by the regulation of multitarget genes expression. Therefore, we checked the main protein expression, such as thymidylate synthase (TS)、p53 and p21 protein. In A549 and H460 cells with wild type of 53, up-regulation of p53 and its down stream regulated p21 protein were demonstrated by Pemetrexed treatment with or without vitamin B12 and folic acid. In H1299 cells with null type of p53, p21 protein is still induced under same treatment as A549 cells. Our data indicate that regulation of p21 expression by Pemetrexed may via two different pathways. In this study, we found vitamin B12 and folic acid supplementation is increasing but not decreasing the Pemetrexed efficacy of antitumor effect of NSCLC cells.
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