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BioMed Research International
Volume 2013 (2013), Article ID 389046, 10 pages
http://dx.doi.org/10.1155/2013/389046
Research Article

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

1Institute of Medicine, Chung Shan Medical University, No. 110, Sec 1, Jianguo N. Road, Taichung 402, Taiwan
2Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 160, Sec 3, Chung-Kang, Taichung 407, Taiwan
3Department of Medicine, School of Medicine, National Yang-Ming University, 155, Sec 2, Lih-Non Street, Shih-Pai 112, Taipei, Taiwan
4Institute of Biomedical Sciences, National Chung Hsing University, No. 160, Sec 3, Chung-Kang, Taichung 407, Taiwan
5Department of Education and Research, Taichung Veterans General Hospital, No. 160, Sec 3, Chung-Kang, Taichung 407, Taiwan
6Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, No. 110, Sec 1, Jianguo N. Road, Taichung 402, Taiwan

Received 23 April 2013; Accepted 8 July 2013

Academic Editor: Ruxana T. Sadikot

Copyright © 2013 Tsung-Ying Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.