Sorcin蛋白高表达与肺癌细胞株NCI-H446多药耐药的关系

Relationship of Sorcin over-expression to multidrug resistance of human lung cancer cell line NCI-H446

关键词:  可溶性耐药相关钙结合蛋白  肺癌  多药耐药  耐药指数

Key words:  soluble-resistance related calcium binding protein (sorcin)  lung cancer  muit-drug resistance  resistance index

摘要:

目的　探讨Sorcin高表达与肺癌细胞NCI-H446多药耐药的相关性。　方法　研究对象为肺癌细胞NCI-H446，以顺铂为诱导药物，建立多药耐药细胞系NCI-H446／CDDP；应用反义核酸技术抑制NCI-H446/CDDP细胞Sorcin的表达建立转染细胞，为反义核酸组，同时设空白对照组。通过RT-PCR及Western-blot分别检测各组细胞中Sorcin在核酸及蛋白水平的表达；MTT法测定NCI-H446组、反义核酸组、NCI-H446／CDDP组3组细胞在不同化疗药物DDP、VCR、ADM、VP-16作用下生存率；用Pearson相关分析Sorcin高表达与肺癌细胞株NCI-H446多药耐药的相关性。　结果　各组细胞中Sorcin在核酸及蛋白水平的表达， NCI-H446／CDDP组与空白对照组比较，差异无显著性意义（P>0.05），NCI-H446组、反义核酸组、NCI-H446／CDDP组各组间比较均具有显著性意义（P<0.05）；NCI-H446/CDDP细胞中Sorcin在核酸及蛋白水平均明显高于NCI-H446细胞，分别为NCI-H446细胞的9.81倍和7.67倍。各组细胞在不同化疗药物作用下IC50：NCI-H446／CDDP组＞反义核酸组＞NCI-H446组，各组间比较差异具有显著性意义（P<0.05）。Pearson相关提示：Sorcin 核酸及蛋白水平的表达与在不同化疗药物作用下各组细胞的IC50值呈负相关（P<0.05）。　结论　Sorcin蛋白的高表达与肺癌多药耐药相关，抑制Sorcin蛋白的表达可以逆转肺癌多药耐药性。

Abstract:

Obsjective　To investigate the relationship of the high expression of sorcin with multidrug resistance in lung cancer cell NCI-H446.　Methods　Lung cancer cell NCI-H446 was object of study, set up cell line NCI-H446／CDDP through cisplatin;Using antisense nucleic acid technology inhibited the expression of sorcin in NCI-H446/CDDP cell, building antisense nucleic acid group, at same time setting up blank control group. RT-PCR and Western-blot were used to analyze the expression of sorcin at mRNA and protein levels in every cell group. MTT was used to three groups cell (NCI-H446 cell group, antisense nucleic acid group, NCI-H446／CDDP group) survival rate in DDP, VCR, ADM, VP-16. Pearson correlation was used to analyze the correlation of the high expression of sorcin with multidrug resistance in lung cancer cell NCI-H446.　Results　Comparison with the expression mRNA and protein of sorcin in every groups, the result showed: comparing NCI-H446/CDDP group with blank control group has no statistical significance (P>0.05), In tercomparison in NCI-H446 cell group, antisense nucleic acid group, NCI-H446/CDDP group has statistical significance (P<0.05). The expression mRNA and protein of sorcin in NCI-H446/CDDP were obviously higher than it in NCI-H446 cell, 9.81 and 7.67 times respectively. The result of IC50: NCI-H446/CDDP group >antisense nucleic acid group > NCI-H446 cell group, has statistical significance (P<0.05). Pearson correlation to point out: the expression of sorcin in mRNA and protein was negatively correlated to IC50 of the group cells in different chemotherapy drugs. 　Conclusion　The high expression of sorcin is related to multidrug resistance in lung cancer cell, Inhibition of its expression can reverse the drug resistance of lung cancer.