目的:研究p53靶向小分子肿瘤凋亡和p53再生化合物(RITA)联合替莫唑胺(TMZ)对胶质瘤细胞体外生长的影响。方法:培养人胶质瘤细胞株U87并随机分为RITA+TMZ组(5 μmol/L RITA和10 μmol/L TMZ处理)、TMZ组(10 μmol/L TMZ处理)、对照组(不含药物的DMEM处理)。处理后24 h,测定细胞中p53下游细胞周期分子、凋亡分子及侵袭分子的表达量。结果:RITA+TMZ组、TMZ组细胞中p21cip1、Per2、ATM、E-cadherin的蛋白表达量显著高于对照组,CDK4、CDK6、p-Rb、E2F、MDM2、c-myc、ILK、Snail、Slug的蛋白表达量显著低于对照组；RITA+TMZ组细胞中p21cip1、Per2、ATM、E-cadherin的蛋白表达量显著高于TMZ组,CDK4、CDK6、p-Rb、E2F、MDM2、c-myc、ILK、Snail、Slug的蛋白表达量显著低于TMZ组。结论:p53靶向小分子RITA联合替莫唑胺处理胶质瘤细胞能够诱导p53所介导的细胞周期阻滞、细胞凋亡激活以及细胞侵袭抑制。
Objective: To study the effect of p53 targeted small molecule reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the growth of glioma cells in vitro. Methods: Human glioma cell line U87 was cultured and randomly divided into RITA+TMZ group (5 μmol/L RITA and 10 μmol/L TMZ treatment), TMZ group (TMZ 10 μmol/L), and control group (DMEM without drug treatment). After 24 h of treatment, p53 downstream molecule cell cycle molecules, apoptotic molecules and invasive molecules were measured. Results: protein expression of p21cip1, Per2, ATM, E-cadherin in RITA+TMZ group and TMZ group were significantly higher than the control group, the protein expression of CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail, Slug were significantly lower than the control group; the expression of p21cip1, Per2, ATM, E-cadherin in RITA+TMZ group were significantly higher than those of TMZ group, the expression of CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail, Slug were significantly lower than those of TMZ group. Conclusions: p53 targeted small molecule RITA combined with temozolomide treatment of glioma cells can induce p53 mediated cell cycle arrest, apoptosis activation and cell invasion inhibition.