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目的探讨体内外顺铂(DDP)给药后miR-638表达水平及变化,评价miR-638表达在DDP诱导人肺腺癌细胞凋亡中的意义。方法建立荷SPC-A1瘤的BALB/c裸鼠移植瘤模型,经尾静脉注射DDP后,检测各组裸鼠血清miR-638表达水平。体外培养SPC-A1并经DDP作用不同时间后,检测培养上清miR-638表达水平及细胞凋亡率。收集60例肺腺癌患者DDP化疗前后的血清样本,检测miR-638在化疗前后的表达改变情况并分析其与预后的关系。结果体外DDP处理SPC-A1细胞后凋亡率在24、48和72 h时均显著高于同时间点对照组(P均<0.01),且随时间延长显著增高(任意两组间P<0.01);DDP作用后培养上清中miR-638表达水平呈时间依赖性增高,且在24、48、72 h均显著高于相应对照组(P均<0.05);且SPC-A1培养上清中miR-638水平与凋亡率呈正相关(r=0.711,P<0.01);DDP治疗组裸鼠血清miR-638表达水平明显高于生理盐水处理组和未治疗对照组(P均<0.05),而后两组间差异无统计学意义(P>0.05);接受DDP化疗后血清miR-638表达上调的患者总体生存率明显高于表达下调者(P<0.05)。结论 miR-638在体内和体外DDP诱导的人肺腺癌细胞凋亡中均出现表达上调,提示miR-638可能对肺癌DDP化疗中判断预后及疗效观察具有一定价值。
Objective To investigate the expression of miR-638 in vitro and in vivo after cisplatin (DDP) administration and to evaluate the significance of miR-638 expression in apoptosis of human lung adenocarcinoma cells induced by DDP. Methods BALB / c xenografts in nude mice bearing SPC-A1 tumor were established. After DDP injection through tail vein, the expression of miR-638 in each group was detected. After culture of SPC-A1 in vitro and DDP for different time, the expression level of miR-638 in culture supernatant and the rate of apoptosis were detected. Serum samples of 60 patients with lung adenocarcinoma before and after DDP chemotherapy were collected to detect the expression of miR-638 before and after chemotherapy and to analyze its relationship with prognosis. Results The apoptotic rate of SPC-A1 cells treated with DDP in vitro was significantly higher than that of the control group at 24, 48 and 72 h (P <0.01), and significantly increased with time (P <0.01 for any two groups) ). The expression of miR-638 in the culture supernatant after DDP treatment increased in a time-dependent manner, and was significantly higher than that of the corresponding control group at 24, 48 and 72 hours (all P <0.05). In the supernatant of SPC-A1 The level of miR-638 was positively correlated with the apoptosis rate (r = 0.711, P <0.01). The level of miR-638 in DDP treated group was significantly higher than that in saline group and untreated group (all P <0.05) There was no significant difference between the two groups (P> 0.05). The overall survival rate of patients with up-regulated serum miR-638 after DDP chemotherapy was significantly higher than that of those with down-regulated expression (P <0.05). Conclusions miR-638 is upregulated in both DDP-induced and human lung adenocarcinoma cells in vitro and in vivo, suggesting that miR-638 may be of value in the prognosis and efficacy of DDP chemotherapy for lung cancer.