Hypoxia-induced chemotherapy resistance in nasopharyngeal carcinoma CNE2 cell line and its mechanism
AIM: To explore the mechanism of multidrug resistance of nasopharyngeal carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1α ( HIF-1α) and multi-drug resistance related genes. METHODS: Human nasopharyngeal carcinoma cell lines CNE2 cells were exposed to hypoxia. MTT assay was used to investigate resistance index of CNE2 cells to paclitaxel, cisplatin and 5-FU. Cell apoptosis was measured by flow cytometry. The expressions of multidrug resistance gene ( mdr1) , multidrug resistance protein ( MRP1). gene and hypoxia-inducible factor-1α(HIF-1α) at the mRNA and the protein levels analyzed by RT-PCR and Westem-blot technique. RESULTS: After exposed to hypoxia for 48 h, Paclitaxel, Cisplatin and 5-Fu resistance of CNE2 was increased 2.14,1.86 and 1.43 folds than that of in normoxia, respectively. The apoptosis of CNE2 cells in hypoxia was quite decreased after CNE2 exposed to Paclitaxel (8 nmol/L). In the hypoxia group, the expressions of mdr1, MRP1 were stepped up correlating to the degree of hypoxia, especially the prominent increase in the expression of MRP1. Furthermore, they were synchronous with the changes of the expression of HIF-1α. Also the increased expression of mdrl and MRP1gene was observed. CONCLUSION: Resistance of nasopharyngeal carcinoma to chemotherapeutics could be induced by hypoxia. Hypoxia induced the expressions of HIF-la and the related multi-drug resistance genes. HIF-1α and these related multidrug resistance genes could be potential molecular targets for reversing multidrug resistance of nasopharyngeal carcinoma.
NETL
NSTL
万方数据
维普
