辐射促进多药耐药反义寡脱氧核苷酸体内逆转耐药的实验研究

The Ionic Radiation Promoted Improvement of Multidrug Resistance Reversal in vivo by mdr1 Antisense Oligodeoxynucletides

目的:探讨辐射促转染的多药耐药(MDR)基因mdr;反义寡核苷酸(ASON)体内逆转肿瘤耐药的效果。方法:采用耐药细胞株KBv_(200)移植于裸鼠皮下,建立肿瘤耐药模型,肿瘤局部2Gy^(60)Co-γ辐射后1h,瘤内注射脂质体介导的mdr_1 ASON,经长春新碱联合化疗。结果:对照组与联合辐射组、未联合辐射组肿瘤生长曲线差异有显著性(P<0.01),联合辐射组与未联合辐射组肿瘤生长曲线差异有显著性(P<0.01)。对照组与联合辐射组、未联合辐射组肿瘤体积和肿瘤重量差异有显著性(P<0.01),联合辐射组与未联合辐射组肿瘤体积和肿瘤重量差异有显著性(P<0.01)。联合辐射组肿瘤重量抑制率为(80.78±1.9)%,肿瘤体积抑制率为(84.91±2.1)％。结论:辐射促转染的mdr_1 ASON对肿瘤细胞具有较强的耐药逆转作用。

Objective:To investigate the reversal of tumor multidrug resistance (MDR) in vivo by MDR gene mdr, antisense oligodeoxynucletides (ASON) in combination with ionic radiation. Methods: A nude mice model transplanted with resistant cell line KBv200 was established. Mdr1 ASON was injected into tumor in 1 hour after local 2Gy 60Co-γ radiation. The tumor-suppressing rates and tumor-suppressing curves were observed in experimental groups and control group after treatment by vincrstine (VCR). Results: The results showed that the significant differences of tumor growth curves occurred between control group and treated groups (P < 0. 01) , and between treated groups that accepted combined radiation or not (P <0.01) . Significant differences of tumor weight and tumor volume were also observed between the two different treated groups (P <0. 01). The suppressing rates of tumor volume and weight were 84.91±2. 1% and 80.78±1.9% respectively in group accepted combined radiation. Conclusion: The reversal effect of mdr, ASON on the resistance cell line could be strengthened when combined with ionic radiation.