长链非编码RNA UCA1在胃癌多药耐药中的作用研究

目的:研究胃癌耐药细胞及其亲本细胞中长链非编码RNA UCA1的表达差异,探讨UCA1在胃癌多药耐药中的作用。方法:通过实时荧光定量PCR(q RT-PCR)检测胃癌耐药细胞SGC7901/ADR、SGC7901/VCR及其亲本细胞SGC7901中UCA1的表达差异;通过si RNA转染降低SGC7901/ADR中UCA1表达,MTT法检测细胞半数抑制浓度(IC50)的变化,流式细胞仪检测细胞凋亡变化。结果:QRT-PCR结果显示,UCA1在SGC7901/ADR和SGC7901/VCR胃癌耐药细胞表达显著高于SGC7901胃癌亲本细胞;MTT实验表明,干扰UCA1的SGC7901/ADR相对于阴性对照(NC)组的IC50显著降低;凋亡检测结果显示,在相同剂量化疗药物作用下,干扰UCA1后SGC7901/ADR凋亡率显著高于NC组;Western blot证实,干扰UCA1表达可显著降低BCL-2蛋白表达。结论:长链非编码RNA UCA1在胃癌耐药细胞表达显著升高,干扰UCA1表达可明显逆转胃癌耐药,UCA1可作为治疗胃癌耐药的重要分子靶标。

The Role of lncRNA UCA1 on Drug Resistance in Gastric Cancer

Objective:To investigate the differential expression of lncRNA UCA1 in SGC7901/ADR, SGC7901/VCR and SGC7901 gastric cancer cell lines and to explore its role in multi-drug resistance (MDR) of gastric cancer (GC).Methods:The expression level of UCA1 in SGC7901/ADR, SGC7901/VCR and SGC7901 cell lines was obtained by quantitative real-time PCR (qRT-PCR) detection. SiRNA transfection was applied to knockdown UCA1 expression in SGC7901/ADR. The drug sensitivity (IC50) of SGC7901/ADR were detected byMTT assay; apoptosis rates were detected by flowcytometry and the protein expression of Bcl-2 by western blot. Results:QRT-PCR results showed that the expression level of UCA1 in SGC7901/ADR and SGC7901/VCR was significantly higher than that in parental SGC7901 cells. The MTT assay and flow cytometry analysis showed that the drug sensitivity (IC50) and apoptosis rates of SGC7901/ADR were significantly increased compared with negative control (NC) group. Western blot results confirmed that knockdown of UCA1 in SGC7901/ADR can significantly reduce the expression of BCL-2 protein.Conclusion:Long non-coding RNA UCA1 was significantly up-regulated in two MDR GC cell sublines, SGC7901/ADR and SGC7901/VCR. Our findings indicate that UCA1 plays a positive role in the regulation of the MDR phenotype of GC MDR cell sublines and is a potential target to resverse GC MDR.