肺腺癌A_(549)/DDP细胞周期变化及其多药耐药性

Change of Cell Cycle and Resistance of A_( 549) Cells to Cisplatin.

用Fura 2 /AM标记药物敏感的肺腺癌细胞A54 9和抗顺铂药物的肺腺癌细胞A54 9/DDP两种细胞胞内游离Ca2 +,用碘化丙锭 (PI)标记细胞DNA ,检测其胞内Ca2 +的变化及两种细胞增殖能力和细胞周期 .实验结果表明 ,抗药性细胞株A54 9/DDP胞浆内游离Ca2 +的浓度仅为药物敏感细胞株A54 9的 1/ 3左右 ,同时前者的细胞增殖能力较后者明显增强 ,而且细胞周期也明显缩短 .当用BAPTA AM和EGTA或A2 3187和Thapsigargin处理细胞以降低或升高其胞内自由Ca2 +浓度时可改变细胞的生长周期 ,二者也呈现明显差别 .这些结果表明 ,对顺铂产生耐药性的人肺腺癌A54 9/DDP细胞胞内Ca2 +浓度的降低 ,可能影响细胞的增殖 ,缩短细胞的生长周期 ,特别是影响起决定作用的G1期 。

The change of intracellular free Ca 2+ in A 549 cells sensitive and A 549 /DDP cells resistant to the cis dichlorodiammine platinum (cisplatin) were measured by Fura 2/AM, the proliferation ability and cell cycle were measured by propidium iodide(PI) labeling cellular nuclear DNA. The results indicated that the concentration of intracellular free calcium of the sensitive A 549 cells was 2 times higher than that of the resistant A 549 /DDP cells; the proliferation ability of the latter increased significantly than that of the former, the cell cycle also shortened. The proliferation ability and cell cycle of the two cell lines also clearly showed difference by decreasing or increasing their intracellular free calcium concentration if the cells were treated with BAPTA AM or EGTA and A 23187 or Thapsigargin. All of the results demonstrated that the concentration decrease of intracellular free calcium in the A 549 /DDP cells resistant to cisplatin may affect the cellular proliferation, shorten the cellular cycle, which would be helpful to remain the multidrug resistance characteristics of A 549 /DDP cells by specially modulating the cellular decisive G1 of cell cycle.