Experimental on Drug-resistant Effect on Nasopharyngeal Cancer Cells with siRNA-HIF-1α Silencing

Objective To investigate drug-resistant effect in a cisplatin-resistant human nasopharyngeal carcinoma (NPC) cell line CNE2/DDP with HIF-1α silencing. Methods The drug-resistant cell line CNE2/DDP was established by a procedure of the human NPC cell line CNE2 exposed to the medium with repeated sharp high and then low but gradually increasing concentration of cisplatin.Small fragments of HIF-1α RNA were transfected into the cell line CNE2/DDP to silence HIF-1α by transient transfection method.Cell proliferation and apoptosis of cell line CNE2/DDP with HIF-1α silencing were measured by MTS assay and flow cytometry analysis,respectively.Western blot were applied to detect the expression of HIF-1 α and MDR1 in cell line CNE2/DDP. Results The cisplatin-resistant human NPC cell line CNE2/DDP was established successfully and the resistance index was 16.When the concentration of cisplatin was higher than or equal to 1.0 μg/ml,the inhibition rates of cisplatin on CNE2 group and siHIF-1α siRNA group were significantly higher than that on CNE2/DDP group and siCtrl-siRNA group (P<0.05).Similarly,flow cytometry analysis showed that apoptosis in CNE2 group and siHIF-1α siRNA group were significantly higher than that in CNE2/DDP group and siCtrl-siRNA group (P<0.05).Furthermore,Western blot showed that HIF-1α and MDR1 proteins in siHIF-1α siRNA group were significantly lower than those in CNE2/DDP group. Conclusion HIF-1α silenced by siRNA improved the sensitivity of the cisplatin-resistant human NPC cell line CNE2/DDP to cisplatin,and reversed the resistance of CNE2/DDP to cisplatin.