整合素β-1对实体瘤细胞耐药的影响研究

Effect of integrin β-1 on drug-resistance of solid tumor cells

目的 初步探讨粘附分子 β 1整合素对肿瘤耐药的影响。 方法 采用人肺腺癌细胞株A5 49,分别以不同浓度阿霉素诱导建立耐药细胞株 ,采用MTT法检测肿瘤细胞结合纤维粘连蛋白 (FN)及阻断 β 1整合素后对肿瘤细胞耐药的影响。 结果 经致死剂量的阿霉素作用 ,MTT法检测药物敏感的肿瘤细胞抑制率为 97 1% ,耐药细胞株为 45 2 % ;与纤维粘连蛋白结合后 ,药物敏感细胞株抑制率为 68.5 % ,耐药细胞株为 5 6 4% ;阻断 β 1整合素后与纤维粘连蛋白结合 ,药物敏感细胞株抑制率达到 94% ,耐药细胞株为 49 4%。与纤维粘连蛋白结合后 ,肿瘤细胞抑制率明显下降 (P <0 0 5 ) ;阻断 β 1整合素功能后 ,肿瘤细胞抑制率显著上升。结论 肿瘤细胞与细胞外基质作用是造成肿瘤耐药的原因之一 。

Objective To study the effect of the adhesion molecule β 1integrin on the drug resistance of tumor. Methods The drug resistance model of human lung adenocarcinoma cell line was established with adriamycin of different concentrations. The impact of tumor cells after binding to fibronectin and blocking integrin β 1 on the drug resistance of tumor cells was monitored by MTT. Results The inhibition rate of the drug sensitive tumor cells and the rate of the drug resistance cell line were 97.1% and 45.2% after the use of adriamycin at the lethal dose, 68.5% and 56.4% after binding to fibronectin, and 94% and 49.4% after blocking the binding of β 1 integrin to fibronectin, respectively. After binding with fibronectin, the inhibition ratio of tumor cells decreased significantly( P <0.05), but after blocking the binding of β 1 integrin to fibronectin, the inhibition ratio increased significantly( P <0.05). Conclusions The action of cell via matrix is one of the causes for the tumor cells to develop drug resistance which may be reversed by blocking the action between cell and matrix