三氧化二砷对肺癌移植瘤的放疗增敏效应

Radiosensitization effects of arsenic trioxide in lung cancer xenografts

目的:探讨三氧化二砷(As_2O_3)对肺癌移植瘤的放疗增敏作用及其可能机制。方法:在C57BL/6小鼠右前肢腋窝皮下接种Lewis肺癌细胞,建立肿瘤小鼠模型。将40只荷瘤小鼠随机分成4组:对照组(腹腔注射生理盐水0.2 ml);单纯照射组(腹腔注射生理盐水0.2 ml,6 MeV电子线照射,10 Gy);As_2O_3组(2.0 mg/kg,溶于0.2 ml生理盐水中,腹腔注射);As_2O_3+照射组(2.0 mg/kg腹腔注射As_2O_3后,6 MeV电子线照射,10 Gy)。实验结束后,处死各组动物,分离肿瘤,称取瘤质量,计算抑瘤率。用RT-PCR法测定肿瘤组织中VEGF和Ku70 mRNA水平,免疫组织化学法测定肿瘤组织中VEGF和Ku70蛋白的表达。结果:成功建立Lewis肺癌荷瘤小鼠模型。与对照组、As_2O_3组及单纯照射组比较,As_2O_3+照射组的抑瘤率明显增高,而VEGF和Ku70 mRNA和蛋白表达均显著下调(P均<0.05)。结论:As_2O_3能增加肺癌移植瘤的放射敏感性,其辐射增敏作用可能与下调照射后肿瘤组织VEGF和Ku70的表达有关。

OBJECTIVE：To explore the effects of arsenic trioxide on radiosensitivity and the possible mechanism in lung cancer xenografts.METHODS：The tumor-bearing C57BL/6 mouse model was established by injecting Lewis lung cancer cells into right infra-axillary dermis.40 mice were randomized into 4 groups：control group（peritoneal injection 0.9%NS,0.2 ml）;As_2O_3 group（peritoneal injection,2.0 mg/kg,0.2 ml As_2O_3）;irradiation group（peritoneal injection 0.9% NS,0.2 ml ＋ 6MeV Electron Beam,10 Gy）;As_2O_3 ＋ irradiation group（peritoneal injection,2.0 mg/kg,0.2 ml As_2O_3 ＋ 6MeV Electron Beam,10 Gy）.After experiments,mice were sacrificed,then the tumors were separated and weighed.Response to irradiation was evaluated by tumor-inhibiting rate.The expressions of VEGF and Ku70 mRNA were evaluated by RT—PCR. The protein levels of VEGF and Ku70 were measured by immunohistochemical staining.RESULTS：The Lewis lung cancer-bearing model was successfully established in mice.As_2O_3 ＋ irradiation could significantly increase the tumor-inhibiting rate and downregulate the expression of VEGF and Ku70 of irradiated carcinoma xenografts,（Compared with As_2O_3 group or irradiation group,P0.05）.CONCLUSION：Arsenic trioxide could sensitize lung cancer xenografts to ionizing irradiation. This effect was probably mediated by downregulating the expressions of VEGF and Ku70.