Effect of Folic Acid and Vitamin on Pemetrexed Antifolate Chemotherapy in Nutrient Lung Cancer Cells

• Main Authors: Tsung-Ying Yang, Gee-Chen Chang, Shih-Lan Hsu, Yi-Rou Huang, Ling-Yen Chiu, Gwo-Tarng Sheu
• Format: Article
• Language: English
• Published: Hindawi Limited 2013-01-01
• Series: BioMed Research International
• Online Access: http://dx.doi.org/10.1155/2013/389046
• ISSN: 2314-6133; 2314-6141

Pemetrexed (MTA) is a multitargeted antifolate drug approved for lung cancer therapy. Clinically, supplementation with high doses of folic acid (FA) and vitamin B12 (VB12) lowers MTA cytotoxicities. An antagonistic effect of FA/VB12 on MTA efficacy has been proposed. However, patients who receive FA/VB12 show better tolerance to MTA with improved survival. The aims of this study are to investigate the modulation of FA and VB12 on MTA drug efficacy in human nonsmall cell lung cancer (NSCLC) cell lines. The sensitivities of cells, apoptosis, and MTA-regulated proteins were characterized to determine the possible effects of high doses of FA and VB12 on MTA efficacy. MTA has the lowest efficacy under 10% serum conditions. However, supplementation with FA and VB12 individually and additively reversed the insensitivity of NSCLC cells to MTA treatment with 10% serum. The enhanced sensitivities of cells following FA/VB12 treatment were correlated with increasing apoptosis and were specific to MTA but not to 5-fluorouracil (5-FU). Enhanced sensitivity was also associated with p expression level. Our results revealed no antagonistic effect of high doses of FA/VB12 on MTA efficacy in cancer cells grown in nutrient medium. Furthermore, these data may partially explain why supplementation of FA and VB12 resulted in better survival in MTA-treated patients.