泰索帝合并温热对肺腺癌细胞的杀伤效应

Cytotoxic effect of taxotere in combination with hyperthermia on human lung cancer cell line SPC-A-1

目的研究泰索帝合并温热对SPC-A-1肺腺癌细胞的杀伤效应。方法不同浓度(0.05μg/ml～10μg/ml)泰索帝合并温热(39～42℃)作用后,应用MTT法测定其对细胞的杀伤效应,用流式细胞仪和Feulgen染色法检测5μg/ml泰索帝合并41℃对细胞周期影响,并用考马氏亮蓝法观察细胞骨架的形态变化。结果40℃以上温热作用60min,可抑制SPC-A-1细胞生长,其效应随温度的升高逐渐增强,以42℃最明显; 24h后,各组抑制效应均较即时组更明显。泰索帝单独作用对肺癌细胞的杀伤效应在5μg/ml出现,停药后24h杀伤效应有所降低。低浓度泰索帝与39℃～42℃合并可见显著抑瘤协同效应,24h后协同效应仍存在。合并作用可使更多细胞阻滞于分裂期,细胞形态变圆,可出现骨架蛋白凝聚、细胞伸展不良,细胞分裂异常,可见较多微核、多核细胞。结论泰索帝与温热合并有协同效应,可提高泰索帝对SPC-A-1肺腺癌细胞的杀伤效应,降低用药浓度,其机制可能与细胞骨架功能障碍及温热增加膜对药物通透性有关。

Objective To study the cytotoxicity of taxotere combined with hyperthermia in human lung cancer cell line SPC -A -1. Methods Taxotere in combination with hyperthermia （39 -42℃ ） was adminis- tered to SPC -A -1 cells. Survival assay experiments included the exposure of SPC -A -1 cells to taxotere for 24h with heat 39℃, 40℃, 41℃ and 42% for 60 min at the last hour of drug treatment. Cell DNA was assayed by Feulgen staining and FACS. The microtubule structure of SPC - A - 1 cells was analyzed by Coomassie BB. Results Hyperthermia over 40℃ demonstrated inhibitory effect on SPC - A - 1 cells. This effect was enhanced along with the increase of temperature, especially 24h after treatment. Cytotoxicity of taxotere presented at 5 μg/ml and was positively correlated with concentration. Cytotoxicity of low - dose taxotere combined with hyperthermia at 39℃ -42℃ was observed, even at 24h after treatments. More SPC -A -1 cells were blocked at G2/M and tended to be round. Cytoskeleton protein condensed. Many polykaryocytes and micronuclei were observed. Conclusion Taxotere combined with hyperthermia has synergetic effect. Hyperthermia may enhance the cytotoxicity of taxotere on SPC - A - 1 ceils. The synergic molecular mechanism may be involveed in the functional confusion of cytoskeleton and high temperature can increase the amount of intracellular taxotere.