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目的探讨靶向GST-π、polβ的siRNA重组慢病毒在裸鼠体内对人食管鳞癌顺铂耐药株耐药的逆转作用。方法采用皮下注射细胞法建立裸鼠人食管癌细胞细胞EC9706及其耐药细胞EC9706/cDDP移植瘤模型,观察其成瘤性和体内耐药性。利用靶向GST-π、polβ的siRNA重组慢病毒感染具有MDR表型的裸鼠移植瘤,以期达到封闭GST-π、polβ的转录和表达,检测移植瘤细胞对药物的敏感性变化。结果 cDDP联合靶向GST-π的siRNA慢病毒GSTsi2处理组中观察到移植瘤体积与cDDP组及PBS对照组比较,体积显著减小,表明经cDDP联合GSTsi2处理后,可明显恢复移植瘤细胞对cDDP的敏感性。而在cDDP联合靶向polβ的siRNA慢病毒polsi1处理组中移植瘤体积与cDDP及PBS对照组比较无显著差异,移植瘤细胞对cDDP的敏感性无明显改变。结论靶向GST-π的重组慢病毒可有效逆转食管癌细胞的耐药性,靶向polβ的重组慢病毒逆转肿瘤细胞耐药的效果不明显。
Objective To investigate the reversal effect of siRNA targeting GST-π and polβ on the resistance of human esophageal squamous cell carcinoma to cisplatin-resistant strains in nude mice. Methods Human esophageal cancer cell EC9706 and EC9706 / cDDP xenograft model of nude mice were established by subcutaneous injection. The tumorigenicity and drug resistance in vivo were observed. Transfect the transplanted nude mice bearing MDR phenotype with recombinant lentivirus targeting GST-π, polβ in order to achieve the closure of transcription and expression of GST-π, polβ, and to detect the sensitivity of the transplanted tumor cells to drugs. Results Compared with the cDDP group and the PBS control group, the volume of the transplanted tumor was significantly decreased in the cDDP combined with siRNA-targeting GST-π siRNA lentivirus GSTsi2 treatment group, indicating that the cDDP combined with GSTsi2 treatment can significantly restore the transplanted tumor cell pairs cDDP sensitivity. In cDDP combined with polβ targeting polβ siRNA lentiviral polsi1 treatment group, the volume of tumor xenografts compared with cDDP and PBS control group no significant difference in the transplanted tumor cells cDDP sensitivity did not change significantly. Conclusion Recombinant lentivirus targeting GST-π can effectively reverse the drug resistance of esophageal cancer cells. The effect of recombinant lentivirus targeting polβ on reversing the drug resistance of tumor cells is not obvious.