微小RNA-210与胃癌患者治疗的相关性及对胃癌BGC823细胞化疗敏感的影响

Relationship between microRNA-210 and treatment of advanced gastric cancer and its effect on chemosensitivity of gastric cancer BGC823 cells

目的分析microRNA-210与中晚期胃癌患者治疗疗效的关系,并探讨其对胃癌BGC823细胞化疗敏感的影响。方法于86例中晚期胃癌患者作为研究对象,所有研究对象均给予放化疗治疗(6 MV X射线50~60Gy/30 f,5次/周;第1天:奥沙利铂85 mg·m^-2、静脉滴注2 h;第1~14天:替吉奥胶囊80 mg·m^-2、早晚餐后口服,后停药7 d),21 d为1个周期,共治疗4个周期。用RECIST1.1作为疗效评价,根据疗效不同将其分为敏感组和非敏感组。用实时荧光定量逆转录聚合酶链反应法检测治疗前2组血浆和胃癌活检组织microRNA-210水平。针对microRNA-210序列设计microRNA-210-siRNA,将其转染胃癌BGC823细胞,为microRNA-210-siRNA组,并设置NC-siRNA组(转染NC-siRNA)和空白对照组(转染等量生理盐水),用qRT-PCR检测各组microRNA-210鉴定转染效率;用CCK-8法和平板细胞克隆形成实验检测沉默microRNA-210对胃癌BGC823细胞增殖及生长的影响。结果治疗后,敏感组(CR+PR)47例,非敏感组(SD+PD)39例。敏感组血浆和组织microRNA-210分别为2.15±0.33和2.71±0.46;非敏感组血浆和组织microRNA-210分别为4.11±1.07和5.82±1.32,差异均有统计学意义(均P<0.05)。microRNA-210-siRNA组、NC-siRNA组和空白对照组细胞克隆形成率分别为(2.10±0.17)%,(4.35±0.37)%和(4.29±0.34)%,microRNA-210-siRNA组明显低于NC-siRNA组和空白对照组(P<0.05);NC-siRNA组和空白对照组比较差异无统计学意义(P>0.05)。结论低水平microRNA-210中晚期胃癌患者对化疗敏感;沉默microRNA-210可明显提高奥沙利铂-替吉奥抑制胃癌细胞增殖和生长的能力。

Objective To analyze the relationship between microRNA-210 and the clinical effect of combined therapy for advanced gastric cancer,and to explore the effect of microRNA-210 on chemosensitivity of gastric cancer BGC823 cells.Methods Eighty-six patients with advanced gastric cancer were selected as the study subjects.All the subjects were treated with radiochemical therapy(6 MV X-ray 50-60 Gy/30 f,5 times a week;day 1:oxaliplatin 85 mg·m^-2,intravenous drip for 2 h;day 1-14:tegafur capsule 80 mg·m^-2,oral administration after breakfast and dinner,and drug withdrawal for 7 days),21 days for a total of 4 cycles.RECIST 1.1 was used to evaluate the efficacy.According to the different efficacy,the patients were divided into sensitive group and non-sensitive group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect microRNA-210 levels in plasma and biopsy tissues of gastric cancer in the two groups before treatment.MicroRNA-210-siRNA was designed for microRNA-210 sequence and transfected into gastric cancer BGC823 cells,called microRNA-210-siRNA group.NC-siRNA group(transfected NC-siRNA)and blank control group(transfected physiological saline)were set up.qRT-PCR was used to detect the transfection efficiency of microRNA-210 in each group.CCK-8 and plate cell cloning methods were used to detect the effect of silent microRNA-210 on the proliferation and growth of gastric cancer BGC823 cells.Results After treatment,47 cases were in sensitive group(CR+PR)and 39 cases were in non-sensitive group(SD+PD).MicroRNA-210 in plasma and tissue of sensitive group were 2.15±0.33 and 2.71±0.46;microRNA-210 in plasma and tissue of non-sensitive group were 4.11±1.07 and 5.82±1.32,with significant difference(P<0.05).The cell cloning rates of microRNA-210-siRNA group,NC-siRNA group and blank control group were(2.10±0.17)%,(4.35±0.37)%and(4.29±0.34)%,microRNA-210-siRNA group was significantly lower than those of NC-siRNA group and blank control group(P<0.05),but there was no significant difference between NC-siRNA group and blank control group(P>0.05).Conclusion Low-level microRNA-210 is sensitive to chemotherapy in patients with advanced gastric cancer,and silencing microRNA-210 can significantly improve the ability of oxaliplatin-tegiol to inhibit the proliferation and growth of gastric cancer cells.