RAPA联合SAHA对人肺腺癌A549细胞放疗后增殖的影响

Effect of RAPA Combined with SAHA on Proliferation of Human Lung Adenocarcinoma A549 Cells after Radiotherapy

目的观察雷帕霉素(rapaymcin,RAPA)联合辛二酰苯胺异羟肟酸(suberoylanilide hydroxamic acid,SAHA)对人肺腺癌A549细胞放疗后增殖的影响。方法将不同浓度RAPA(0、1、10、100、1000nmol·L^(-1))与SAHA(0、2.5、5、10μmol·L^(-1))交叉组合处理A549细胞24h,采用MTT法检测A549细胞增殖活性;计算联合指数Q,评价两药联合作用效价;计算两药联合作用下细胞生长抑制率为10%时的联合用药浓度IC10。采用该浓度与放疗联合,细胞克隆实验检测两药联合对A549细胞放疗后细胞存活分数(SF)的影响。结果 RAPA、SAHA对A549细胞的抑制作用呈浓度依赖性,与单药组相比,两药联合作用24h后对A549细胞增殖抑制率均显著提高(P<0.05)。RAPA+SAHA联合放疗组的A549细胞存活分数为(21.1±7.0)%,与单纯放疗组的(67.8±6.3)%、RAPA联合放疗组的(43.1±7.2)%和SAHA联合放疗组的(58.5±1.2)%相比,均显著降低(P<0.05)。结论 RAPA与SAHA联合用药浓度IC10对人肺腺癌A549细胞具有放疗增敏作用。

Objective To observe the effect of rapamycin（RAPA）combined with suberoylanilide hydroxamic acid（SAHA）on the proliferation of human lung adenocarcinoma A549 cells after radiotherapy.Methods A549 cells were treated with RAPA（0,1,10,100,1000nmol/L）,SAHA（0,2.5,5,10μmol·L-1）,or their combination for 24 hours.The proliferation of cells was measured by MTT assay.The combination index Q value was calculated to evaluate the combined effect of RAPA and SAHA.Moreover,the 10%inhibitory concentration（IC10）of the combination of two drugs was calculated.Then,the survival fraction（SF）of A549 cells after radiotherapy and combined treatment with RAPA and SAHA at IC10 was detected by cell cloning assay.Results Both RAPA and SAHA suppressed the proliferation of A549 cells in a dose dependent manner.Compared with single treatment with RAPA or SAHA,the suppression rate was significantly increased by their combination（P0.05）.In addition,the SF value in RAPA＋SAHA＋radiotherapy group（21.1±7.0）% was markedly lower than that in radiotherapy group（67.8±6.3）%,RAPA radiotherapy group（43.1±7.2）% or SAHA＋radiotherapy group（58.5±1.2）%（P0.05）.Conclusion The IC10 of combination of RAPA and SAHA can enhance the sensitization of A549 cells to radiotherapy.