STAT3反义寡核苷酸对肺腺癌裸鼠移植瘤辐射增敏的研究

目的：探讨STAT3反义寡核苷酸（antisense oligodeoxynucleotide，ASODN）对肺腺癌裸鼠移植瘤辐射增敏的影响，为提高恶性肿瘤的辐射敏感性提供新的思路和方法。方法建立裸鼠体内肺腺癌移植瘤动物模型，待瘤体直径＞0.5 cm后，瘤内多点注射STAT3 ASODN，给药剂量：15 mg/kg，1次/d，连续2周，给药后2 h联合γ射线局部照射总剂量20 Gy，每次2 Gy，每周5次，连续2周，照射剂量率0.75 Gy/min，定期测量肿瘤体积，绘制肿瘤生长曲线；测量肿瘤质量，计算抑瘤率；记录存活情况，估算生存率，绘制生存曲线，计算总生存期；免疫组化检测肿瘤组织细胞内STAT3蛋白表达变化情况；Western Blot 检测肿瘤组织内 P-STAT3、Bcl-xL、CyclinD1蛋白表达情况。结果反义（antisense，AS）＋照射（irradiation，IR）组肿瘤体积治疗第8天开始明显小于其余各组肿瘤体积（P＜0.05）；AS＋IR组的抑瘤率为68.4%，高于IR组与AS组的之和；AS＋IR组的平均总生存期为（28.38±0.96）d，明显高于IR组及无义（nonsense，NS）＋IR组（P＜0.005）；STAT3蛋白及其下游Bcl-xL、CyclinD1蛋白表达变化明显下降， STAT3蛋白磷酸化水平也降低。结论 STAT3反义寡核酸能够增强肺腺癌裸鼠移植瘤的辐射敏感性，具有良好的放疗增敏剂临床应用开发前景。

Study on the radiosensitization of STAT3 antisense oligonueleotides on lung adenocarcinoma in nude mice

Objective To investigate the STAT3 antisense oligodeoxynucleotides （ASODN） radiosensitization on lung adenocarcinoma in nude mice, to explore new ideas and approaches to increase the radiosensitivity of malignant tumor. Methods Establishment lung adenocarcinoma xenografts in nude mice animal models, the tumor diameter greater than 0.5 cm, were injected STAT3 ASODN intratumoral multi-point, dosage：15 mg/kg, for 2 weeks, after administration of 2H combined with gamma ray local irradiation, irradiation dose of 20 Gy, 2 Gy each time, 5 times a week, for 2 weeks, according to radiation dose rate 0.75 Gy/min, regular measurement of tumor volume, tumor growth curve; measuring tumor weight inhibitory rate was calculated; recording survival, estimating survival, survival curves plotted to calculate overall survival;immunohistochemical detection of tumor cells STAT3 protein expression changes; Western Blot detection of tumor tissue P-STAT3, Bcl-xL, CyclinD1 protein expression. Results AS＋irradiation treatment group tumor volume was smaller than the rest groups began eighth days of tumor volume （P〈0.05）, STAT3 ASODN combined with radiation can significantly delay tumor growth;the tumor inhibition rate of AS＋irradiation group reach 68.4%, higher than the the sum of simple irradiation group and simple ASODN administration group; AS＋irradiation group, the average overall survival was （28.38＆#177;0.96） days, significantly higher than the irradiation group and NS＋irradiation group （P〈0.005）;STAT3 and its downstream protein Bcl-xL, CyclinD1 protein expression was significantly decreased, STAT3 phosphorylation levels were also reduced. Conclusion STAT3 antisense oligonucleotide can enhance the radiosensitivity of lung adenocarcinoma in nude mice, has good radiosensitizer clinical application and nbsp development prospects.