TIPE2抑制AP-1蛋白增加人非小细胞肺癌细胞系NCI-H1975化疗敏感性的机制研究

TIPE2 sensitizes CDDP to human non-small cell lung cancer cell line NCI-H1975 by suppressing AP-1

目的:探讨TIPE2增强非小细胞肺癌细胞系NCl-H1975化疗敏感性及其机制。方法:非小细胞肺癌系NCIH1975转入TIPE2慢病毒载体后,加入CDDP后使用CCK-8测量IC50值,凋亡细胞用Annexin V/FITC和PI凋亡检测试剂盒进行检测,Western blot检测转染TIPE2后AP-1及MDR-1的蛋白表达量,实时荧光定量PCR检测转染TIPE2后IL-1、IL-6及TNF-αmRNA水平。结果:(1)TIPE2降低非小细胞肺癌系NCI-H1975细胞IC50值(P<0.001);(2)TIPE2增加非小细胞肺癌系NCI-H1975细胞对CDDP的凋亡率(P<0.05);(3)TIPE2可显著降低非小细胞肺癌系NCI-H1975细胞中AP-1及MDR1的表达量;(4)TIPE2可显著降低非小细胞肺癌系NCI-H1975细胞中IL-1、IL-6及TNF-αmRNA水平的表达(P<0.01)。结论:TIPE2可能通过抑制AP-1蛋白增加非小细胞肺癌细胞系NCl-H1975对CDDP的化疗敏感性。

Objective： To investigate the chemosensitivity of TIPE2 in enhancing non-small cell lung cancer cell line NClH1975 and its mechanisms. Methods： TIPE2 lentiviral vector was transfected into NCI-H1975. IC50 was measured by CCK-8 method after treated with CDDP. Apoptotic cells were detected by Annexin V/FITC and PI apoptosis detection kit. The expression of AP-1 and MDR-1 were measured using Western blot after TIPE2 transfected. The mRNA expression of IL-1,IL-6 and TNF-α were measured using Real-time PCR after TIPE2 transfected combined with CDDP administration. Results：（ 1） TIPE2 reduces the values of IC50 of NCIH1975 cells for CDDP（ P〈0. 001）.（ 2） TIPE2 increases the apoptosis rate of NCI-H1975 cells when treated with CDDP（ P〈0. 05）.（ 3） TIPE2 significantly reduces the expression of AP-1 and MDR1 in NCI-H1975 cells when treated with CDDP.（ 4） TIPE2 reduces the mRNA expression of IL-1,IL-6 and TNF-α in NCI-H1975 cells when treated with CDDP（ P〈0. 01）. Conclusion： TIPE2 may increase the chemosensitivity of non-small cell lung cancer cell line NCl-H1975 to CDDP by inhibiting AP-1 protein.