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目的:探讨用反义技术抑制mdr1基因对放射治疗宫颈癌移植瘤的影响。方法:研究分脂质体组、正义寡核苷酸组和反义寡核苷酸组;用RT-PCR检测宫颈癌移植瘤组织放射治疗前后mdr1表达水平的变化。测定各组肿瘤瘤重,计算抑瘤率。用RT-PCR和免疫组织化学法测定VEGF和Ku70的表达。结果:mdr1反义寡核苷酸能有效地抑制mdr1基因表达,经脂质体介导的mdr1反义寡核苷酸作用的宫颈癌移植瘤经射线照射后其抑瘤率较正义寡核苷酸组及单纯照射组明显增加,VEGF蛋白和Ku70表达显著下调,与各对照组有显著差异(P<0.05)。结论:mdr1反义寡核苷酸通过抑制mdr1基因降低宫颈癌移植瘤的放射抗性。其辐射增敏作用可能与下调照射后肿瘤组织VEGF和Ku70表达有关。
OBJECTIVE: To investigate the effects of mdr1 gene silencing on the transplanted tumor of cervical cancer by radiotherapy. Methods: The liposome group, the sense oligonucleotide group and the antisense oligonucleotide group were studied. The expression of mdr1 in cervical cancer tissues was detected by RT-PCR before and after radiotherapy. Tumor weight was measured in each group, and the inhibition rate was calculated. The expression of VEGF and Ku70 was determined by RT-PCR and immunohistochemistry. Results: mdr1 antisense oligonucleotide could effectively inhibit the expression of mdr1 gene. The inhibitory rate of mdr1 antisense oligonucleotide was lower than that of the sense oligonucleotide The levels of VEGF and Ku70 were significantly down-regulated in acid group and irradiation group (P <0.05). Conclusion: mdr1 antisense oligonucleotide can reduce the radioresistance of cervical cancer xenografts by inhibiting mdr1 gene. Its radiosensitization may be related to down-regulation of VEGF and Ku70 expression in tumor tissue.