Effect Of Naa10p Expression Levels On The Sensitivity Of Oral Squamous Cell Carcinoma Cells To Cisplatin

Object:By studying the expression levels of Naa10p in oral squamous cell carcinoma（OSCC）cell line Cal-27,cisplatin-resistant OSCC cell line Cal-27/CDDP,and transplanted tumor tissue of OSCC nude mice,to investigate the function and potential mechanism of Naa10p on cisplatin chemosensitivity in OSCC.Methods:Western Blot and q RT-PCR were used to detect the expression level of Naa10p in Cal-27/CDDP cells and control cells Cal-27.Lentiviral system was used to establish OSCC cell line Cal-27cells of stable interference or overexpression of Naa10p.After Naa10p expression changes,the effect of cisplatin on the growth inhibition of Cal-27 cells was observed,and Western Blot was used to detect the differences in the expression of drug resistance-related molecules P-gp and Bcl-2 in each group of cells.Cal-27/CDDP and Cal-27 cells were inoculated subcutaneously in the right abdomen of female nude mice aged 4-6 weeks,the volume and weight of the tumor were observed and the growth curve was drawn.The expression of Naa10p in tumor tissues of cisplatin-resistant group and control group was detected by Western Blot.Results:1.Compared with the control cell Cal-27,the expression level of Naa10p in Cal-27/CDDP cells was significantly reduced,and the difference was statistically significant（P<0.01）.2.The OSCC cell line Cal-27-LV-sh Naa10p that stably interferes with Naa10p and the OSCC cell line Cal-27-LV-Naa10p that stably overexpresses Naa10p were successfully constructed.3.When the concentration of CDDP was in the range of 0.1,0.5,1,2,4,8μg/m L and the action time of CDDP remained unchanged for 72 h,the strong inhibitory effect on the proliferation of Cal-27 cells was revealed as the CDDP drug concentration increased.Compared with the control group,the growth inhibition rate of Cal-27-LV-sh Naa10p group was significantly reduced（P<0.05）.The growth inhibition rate of Cal-27-LV-Naa10p group was significantly higher than that of control group（P<0.05）.There was no significant difference between LV-NC group and parent group（P>0.05）.4.The IC₅₀ value of CDDP in Cal-27-LV-sh Naa10p group was higher than that of the control group（P<0.05）,and the IC₅₀ value of CDDP in Cal-27-LV-Naa10p group was lower than that of the control group（P<0.05）.5.Compared with the control group,the expression levels of drug resistance molecules P-gp and Bcl-2in Cal-27-LV-sh Naa10p cells were significantly increased（P<0.05）,while the expression levels of P-gp and Bcl-2 proteins in Cal-27-LV-Naa10p cells were significantly decreased（P<0.05）.6.The tumor volume and tumor weight in the Cal-27/CDDP group were significantly higher than those in the Cal-27 group（P<0.05）.7.The expression level of Naa10p in the tumor tissues of nude mice in the Cal-27/CDDP group was significantly lower than that in the Cal-27 group（p<0.05）.Conclusion:1.The expression of Naa10p in Cal-27/CDDP cell line and tumor tissue of Cal-27/CDDP nude mice decreased significantly,and Naa10p was related to cisplatin chemotherapy resistance.2.Down-regulating the expression of Naa10p can reduce the sensitivity of Cal-27 cell to cisplatin,while up-regulating the expression of Naa10p can enhance the sensitivity of Cal-27 cell to cisplatin.3.Interference with Naa10p could significantly enhance the expression of P-gp and Bcl-2,while overexpression of Naa10p could significantly reduce the expression of P-gp and Bcl-2.