摘要
目的探索蛋白磷酸酶2A(PP2A)抑制剂LB-100对宫颈癌细胞Ca ski辐射敏感性的影响。方法 Ca ski(宫颈癌细胞株)及CCD 841CoN(正常小肠上皮细胞株)给予不同浓度梯度(0~100μmol/L)LB-100处理24h后,以CCK-8法检测细胞活性,筛选最佳药物作用浓度。在此药物浓度下,以对照(PBS)、单纯LB-100、单纯辐照及LB-100联合辐照等方式处理细胞(辐照剂量为0、2、4、6Gy),通过平板克隆实验分别观察LB-100对Ca ski和CCD 841CoN辐射敏感性的影响;再以相同的方式处理(细胞辐照剂量为6Gy),通过流式细胞术检测凋亡及细胞周期,初探LB-100增强Ca ski辐射敏感性的机制。结果 LB-100对Ca ski及CCD 841CoN的抑制作用呈药物剂量依赖性;2.5μmol/L LB-100增强Ca ski细胞辐射敏感性,但对CCD 841CoN的辐射敏感性无显著影响;LB-100联合辐照处理促进Ca ski细胞凋亡,LB-100联合辐照组细胞凋亡率与单纯辐照组比较差异有统计学意义[(8.76±1.02)%vs.(4.65±0.72)%,P<0.01];LB-100可下调Ca ski细胞G0/G1期所占比例,LB-100联合辐照组与单纯辐照组比较差异有统计学意义[(19.87±2.54)%vs.(30.73±1.18)%,P<0.05]。结论 PP2A抑制剂LB-100通过促进凋亡、影响细胞周期,增强了人宫颈癌细胞株Ca ski的辐射敏感性,同时,其对正常肠上皮细胞CCD 841CoN无辐射增敏作用,有望成为临床上增强宫颈癌放射治疗疗效的辅助药物。
Objective To investigate the effect of LB-100,an inhibitor of protein phosphatase 2A（PP2A）,on the radiosensitivity of cervical cancer cell line Ca ski.Methods The cell lines Ca ski（cervical carcinoma cell line）and CCD 841CoN（human normal intestinal epithelial cell line）were exposed to LB-100（0to 100μmol/L）for 24 h.CCK-8assay was used to analyze the cell viability and then the best drug concentration screened out.At this drug concentration,we treated Ca ski and CCD 841 CoN with PBS,LB-100 only,radiation only and LB-100 plus radiation（radiation dose：0,2,4,6Gy）,to observe the radiosensitivity of LB-100 on Ca ski and CCD 841 CoN respectively through clonogenic assay.Then we investigated the mechanism by which LB-100 enhanced the radiosensitivity of Ca ski through detection of cell apoptosis and cell cycle via flow cytometry.Results LB100 showed modest dose-dependent inhibition of Ca ski and CCD 841 CoN cells;LB-100（2.5μmol/L）enhanced the radiosensitivity of Ca ski,while there was no radiosensitization on CCD 841 CoN cells;LB100plus radiation enhanced the apoptosis of Ca ski,and there was a statistically significant difference in apoptosis rate between LB-100 plus radiation group and radiation only group[（8.76±1.02）% vs.（4.65±0.72）%,P〈0.01];LB-100 reduced the proportion of Ca ski in G0/G1 phase,there was a statistically significant difference between LB-100 plus radiation group and radiation only group [（19.87±2.54）% vs.（30.73±1.18）%,P〈0.05].Conclusion PP2 Ainhibitor,LB-100 enhances the radiosensitivity of the cervical cancer cell Ca ski,by inducing apoptosis and influencing the cell cycle distribution.And at the same time,it has no effect on radiosensitivity of the normal intestinal epithelial cell line CCD 841 CoN,indicating that LB-100 would be a kind of adjuvant drug to enhance clinical radiotherapy effect of cervical cancer.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2017年第3期303-307,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
