摘要
目的 研究肿瘤细胞与基质粘附对肿瘤耐药性的影响 ,并探讨其机制。方法 应用MTT法研究A5 4 9 ADR耐药细胞与基质成分纤维粘连蛋白 (FN)结合对药物敏感性的影响 ;采用TUNEL法检测细胞凋亡 ,采用流式细胞术观察bcl 2和Bax基因表达。结果 A5 4 9 ADR细胞与FN结合后 ,其耐药性明显增加 (抑制率为 10 2 7% ,对照组为 4 6 0 1% ,P <0 .0 1) ,用抗 β 1整合素抗体阻断其与FN结合 ,其对药物的敏感性又恢复至对照水平 (抑制率为 4 0 86 % ,与对照组比P <0 .0 5 ) ;A5 4 9 ADR细胞与FN结合后 ,bcl 2基因蛋白表达上升 (6 2 0 8% ) ,Bax表达降低 (14 79% ) ,凋亡率 (8 74± 1 0 1) %显著降低 ,对照组为 (16 38±1 0 7) %阻断其与FN结合 ,bcl 2表达明显下降 (2 3 5 9% ) ,而Bax表达上升 (75 83% ) ,凋亡率也升至 (17 2 4± 1.75 ) % (与对照组比P <0 .0 5 )。结论 肿瘤细胞与基质成分结合可上调Bax和下调bcl 2基因表达 ,增强肿瘤细胞的抗凋亡能力 ,从而增加肿瘤耐药性。
Objective To investigate the effects of cell matrix adhesion on drug resistance of tumor cells.Methods MTT test was conducted to study the effects of adhesion between A549 ADR tumor cells and fibronection on sensitivity to anti cancer drugs,the expression of bcl 2 and Bax gene protein was analyzed by flow cytometry.Results The extent of drug resistance decreased to control levels after the binding was blocked by using anti β1 integrin antibody.The expression of bcl 2 protein was increased and the Bax protein was decreased when the tumor cell binds to fibronectin,the rate of apoptosis was also significantly decreased when the tumor cell binds to fibronectin and increased after blocked by antiβ 1 integrin antibody.Conclusion Adhesion of tumor cells with fibronectin can increase drug resistance of tumor cells probably by regulating the expression of apoptosis related genes and the rate of apoptosis.
出处
《重庆医学》
CAS
CSCD
2003年第6期704-705,共2页
Chongqing medicine
基金
国家自然科学基金资助项目 (30 1 71 0 67)
关键词
肿瘤细胞
粘附
耐药
tumor cell
adhesion
drug resistance
