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作 者:王晓艳[1] 华东[1] 李莉华[1] 高琪 郭子健[1]
机构地区:[1]苏州大学附属第四医院肿瘤研究所,江苏省无锡市214062 [2]江苏省血吸虫病寄生虫病防治研究所,江苏省无锡市214062
出 处:《实用医学杂志》2011年第17期3109-3112,共4页The Journal of Practical Medicine
基 金:无锡市卫生局项目(编号:XM1012)
摘 要:目的:通过观察慢病毒介导的siRNA沉默Med19基因对人乳腺癌裸鼠成瘤的影响,探讨Med19在乳腺癌发生发展中的作用。方法:利用前期已稳定感染Med19-siRNA慢病毒载体的人乳腺癌MCF-7细胞,采用Westernblotting方法检测Med19蛋白的沉默效果。稳定感染Med19-siRNA慢病毒载体的人乳腺癌MCF-7细胞接种于BALB/c裸鼠背侧皮下,观察裸鼠成瘤情况和移植瘤生长情况,并绘制生长曲线。以慢病毒空载体感染组作为阴性对照组。结果:所构建的Med19-siRNA慢病毒载体能有效抑制MCF-7细胞Med19蛋白的表达,蛋白表达水平下降了62%,Med19基因沉默组较空载体慢病毒感染组瘤体生长速度慢(t值分别为4.843、6.291、5.317,均P<0.01),肿瘤终体积分别为(620.08±263.07)mm3和(1406.77±351.14)mm3,终重量分别为(0.20±0.18)g和(0.67±0.27)g,差异有统计学意义(t值分别为4.399、3.615,均P<0.01)。结论:Med19基因沉默能有效抑制人乳腺癌裸鼠成瘤和移植瘤生长,表明Med19在乳腺癌发生发展中起到重要作用,并有可能成为乳腺癌靶向治疗的潜在靶点。Objective To study the influence of silencing Medl9 by lentivirus-mediated RNA interference on the tumor growth of human breast cancer cells in nude mice, and to investigate the effects of Med19 on the oncogenesis and progression of breast cancer. Methods Human breast cancer MCF-7 cells steady infected with lentiviruses delivering small interfering RNA (siRNA) against Medl9 gene had been constructed. Western blotting was used to detect the silence of Med19 protein. Then the MCF-7 cells were injected subcutaneously into the back of BALB/c nude mice (KD group). Tumorigenicity and the growth of transplanted tumor in nude mice were observed. Growth curves were plotted based on mean tumor volume in each experimental group at the indicated time points. Meanwhile, the negative control group (NC group) which MCF-7 cells steady infected with lentiviruses delivering negative control sequence was set up. Results The constructed Med19-siRNA lentivirus vector could suppress the expression of Med19 protein in MCF-7 cells effectively, and the level of Medl9 protein was decreased by 62%. As compared with that in NC group, the tumor growth velocity in KD group was slower (t = 4.843, 6.291, 5.317, respectively, all P 〈 0.01). The final weights of tumor in KD group and NC group were (0.20 ± 0.18) g and (0.67 ± 0.27)g, respectively; and the final volume were (620.08 ± 263.07) mm3 and(1 406.77 ±351.14)mm3 ,respectively (t = 4.399, 3.615, respectively, all P 〈 0.01 ). Conclusion The silencing Medl9 gene can strongly suppress the tumor formation and transplanted tumor growth of human breast cancer in nude mice, which suggests that Med19 may play an important role in the oncogenesis and progression of breast cancer, and may constitute a potential therapeutic target in this disease.
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