Relationship Between The Signal Pathway Of Folate Metabolism And Drug-resistance In Nasopharyngeal Carcinoma Cells

Nasopharyngeal carcinoma is a common malignant tumor in Otolaryngology-head and neck surgery. The main choice of treatment is radiation for primary lesion and lympho node. The chemotherapy could improve the prognosis. However, drug-resistance frequently happened during the chemotherapy, and the mechanism of drug -resistance become crucial points. Our previous study had revealed that FOLR1 played an important role in drug-resistance of nasopharyngeal carcinoma. Therefore, it is important to detect the signal pathway of folate metabolism in drug-resiatnce nasopharyngeal carcinoma.Objectives:To explore the relationship between the key genes of folate metabolism pathway (FOLR1, DHFR, SHMT and TS ) and drug-resistance of nasopharyngeal carcinoma, and elucidate the mechanism of drug- resistance in nasopharyngeal carcinoma.Methods:1.The CNE1 and CNE1/Taxol were growing in the medium with or without folic acid. The growth inhibition rates of cells without folic acid were determined using the colony formation assay.2.The expression of FOLR1, DHFR, SHMT and TS genes were detected by semi-quantitative RT-PCR in CNE-1,HNE-2 and paclitaxel-resistance cells (CNE-1/Taxol,HNE-2/Taxol).3.The expression of FOLR1 in nasopharyngeal carcinoma tissues and normal nasopharyngeal epithelial tissues was detected using immunohisto- chemistry.Results:1.The colony inhibition rates of paclitaxel-resistance cells which grew in the medium without folic acid were higher than its parental cells grew in the medium without folic acid (P<0.05). The growth of paclitaxel -resistance cells was much more dependent to folic acid.2.Compared with parental nasopharyngeal carcinoma cells, the significantly higher expression of FOLR1, DHFR, SHMT in CNE-1/Taxol and HNE-2/Taxol were verified by semi-quantative RT-PCR. In the meantime, the results also showed the changes of key enzyme in the folate metabolism may relate to the paclitaxel -resistance in nasopharyngeal carcinoma.3.FOLR1 expression was not detected in normal nasopharyngeal tissues using immunohistochemistry, but lower expression level was found in nasopharyngeal carcinoma tissues, and positive rates ranged from 0% to 42% (average rate at 23.85±13.89%). The significant correlation was revealed between positive expression rates and clinical stages in nasopharyngeal carcinoma (r=0.9345, P<0.01). The positive expression of advanced nasopharyngeal carcinoma was higher than early tumor.Conclusions:1 .The growth of paclitaxel-resistant nasopharyngeal carcinoma cells was much more dependent on folic acid than corresponding parental cells.2.FOLR1, DHFR, SHMT and TS which are the Key enzyme in the folate metabolism related to paclitaxel-resistance in nasopharyngeal carcinoma cells.3.FOLR1 gene may become the target molecules in the treatment of nasopharyngeal carcinoma.