| 摘要: |
| 目的探讨STAT3反义核酸对肺腺癌辐射敏感性的影响。方法以本室自行设计的STAT3反义核酸转染肺腺癌A549细胞，分别接受4、8、12、16、20 Gy 60Co γ射线照射，CCK-8法检测细胞存活率，流式细胞术检测细胞早期凋亡。建立局部照射荷瘤小鼠模型，瘤内多点注射STAT3反义核酸，给药剂量15 mg/kg,连续2周，给药后2 h以60Co γ射线局部照射，照射剂量20 Gy，每次2 Gy，每周5次，连续2周，照射剂量率1 Gy/min。计算肿瘤体积、肿瘤生长延缓时间、相对生长速率、生长抑制率、q值，测量肿瘤质量。结果 体外实验结果表明，与单独照射组相比，反义STAT3联合照射能降低A549细胞的存活率，增加细胞早期凋亡；体内实验结果表明反义STAT3联合肿瘤局部照射能明显减慢移植瘤的生长速度。结论反义STAT3既具有化疗效果，又具备放疗增敏作用，对提高肿瘤的放疗效果有良好的开发前景。 |
| 关键词: 反义寡核苷酸类 STAT3 辐射增敏药 肺腺癌 |
| DOI：10.3724/SP.J.1008.2011.0359 |
| 投稿时间：2011-04-06修订日期：2011-04-11 |
| 基金项目:国家自然科学基金(30470415，30800284). |
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| Role of STAT3 antisense nucleic acid in promoting radiosensitivity of A549 cells |
| SUN Ding,ZHU Bao-rang,GAO Fu,LI Bai-long,CHENG Ying,CAI Jian-ming,CUI Jian-guo * |
| (Department of Radiation Medicine, Faculty of Navy Medicine, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| ObjectiveTo investigate the influence of self-designed STAT3 antisense oligodeoxynucleotides (STAT3 ASODN) on irradiation sensitivity of lung adenocarcinoma. MethodsLung adenocarcinoma cells were exposed to different doses of irradiation (4, 8, 12, 16, and 20 Gy 60Co γ) after transfected with STAT3 ASODN. The survival rates of cells in each group were evaluated by CCK-8 assay. Early apoptosis of cells was observed by FACS. Local irradiation models were established with tumor-bearing mice. STAT2 ASODN was intratumorally injected for two weeks at a dose of 15 mg/kg, and 2 h after injection the animals were locally irradiated with 60Co γ(totally 20 Gy, 2 Gy each time, 5 times each week for 2 weeks, with a irradiation rate of 1 Gy/min). The following parameters were observed, including the tumor size, delay of tumor growth, relative growth rate, growth inhibition rate, q value, and tumor mass. ResultsIn vitro experiment showed that compared with irradiation alone, combination of irradiation with STAT3 ASODN significantly decreased the survival rate and increased the early apoptosis rate of A549 cells. In vivo experiment found that combination of STAT3 ASODN with local irradiation greatly inhibited the growth rate of lung adenocarcinoma xenografts (q=1.27).ConclusionSTAT3 ASODN not only possess chemotherapeutic effect, but also can improve the sensitivity of tumor cells, making it a promising agent for future research and clinical application. |
| Key words: antisense oligonucleotides STAT3 radiation-sensitizing agents lung adenocarcinoma |
