摘要
目的 探讨多西紫杉醇对肺腺癌多药耐药细胞A5 49/CDDP及其亲代细胞的生长抑制作用及其抗肿瘤作用机制。方法 应用MTT比色法和透射电镜等方法,观察A5 49/CDDP及其亲代细胞在多西紫杉醇作用后,细胞生长曲线、生长抑制率及形态学等方面的变化。结果 MTT比色结果表明,多西紫杉醇对A5 49/CDDP细胞及其亲代细胞具有明显的生长抑制作用,并且在0 1～2 μg/ml剂量范围内存在剂量及时间依赖关系。A5 49/CDDP细胞在多西紫杉醇作用12～2 4h较亲代细胞敏感(P <0 0 1) ,在48h开始表现出其药物耐受性(P <0 0 1) ,在72h则与亲代细胞间无显著性差异(P >0 0 5 ) ;透射电镜观察结果发现,A5 49/CDDP细胞及其亲代细胞的胞质内空泡均明显增多,微绒毛减少甚至消失,线粒体出现肿胀甚至空泡化,同时,还存在少数凋亡小体和脱落的不含细胞器成分的细胞质。结论 多西紫杉醇对肺腺癌多药耐药细胞及其亲代细胞均具有明显的生长抑制作用,并可能通过诱导肿瘤细胞坏死、凋亡和胞质自切,从而发挥其细胞毒作用。
Objective To investigate the mechanisms of docetaxel on human lung adenocarcinoma multidrug-resistant cell A549/CDDP and its parental cells A549. Methods Microculture tetrazolium assay (MTT)and transmission electron microscope(TEM) were applied to observe growth curve, inhibition rate, and cell morphological changes after A549/CDDP and A549 cells treated with docetaxel. Results Docetaxel could inhibit growth of human lung adenocarcinoma cells A549/CDDP and A549 both in a time- and a dose-dependent manner at the dose range of 0.1-2 μg/ml. Compared with A549 cell, A549/CDDP cell was more sensitive in 12-24 h, less sensitive in 48 h, and of no statistical difference in 72 h. Meanwhile, vacuoles increasing,microvilli decreasing,mitochondria swollen,a few apoptotic bodies and cytoplasm without organelles were observed both in A549/CDDP and A549 cells by TEM. Conclusion The growth inhibition and anticancer effects of docetaxel may be due to its ability to induce tumor cells necrosis, apoptosis and autoschizis.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2005年第7期610-613,共4页
Journal of Third Military Medical University
基金
国家自然科学基金资助项目 ( 30 2 0 0 119)
中国博士后科学基金资助项目 ( 2 0 0 30 3336 5)~~
关键词
多西紫杉醇
肺腺癌
多药耐药
胞质自切
docetaxel
lung adenovarcinoma
multidrug resistance
autoschizis
