海嘧啶对肺腺癌多药耐药细胞A549/T及其亲代细胞的作用观察和机制的初步研究

目的:探讨海嘧啶对肺腺癌多药耐药细胞A549/T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(mincroculturetetrazolium assay,MTT)比色法和光镜观察等方法,观察A549/T及其亲代细胞在海嘧啶作用后,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,海嘧啶对A549/T细胞及其亲代细胞具有明显的生长抑制作用,并且在10~100μg/ml剂量范围内存在剂量及时间依赖关系。A549/T细胞在海嘧啶作用12~24 h较亲代细胞敏感(P<0.01),在48 h开始表现出其药物耐受性(P<0.01),在72 h则与亲代细胞间无显著性差异(P>0.05);光镜观察结果发现,A549/T细胞及其亲代细胞的胞质内空泡均明显增多,出现细胞核固缩,或碎裂形成大小不等的核碎片,最后可见细胞死亡后的残骸。结论:海嘧啶对肺腺癌多药物耐药细胞及其亲代细胞均具有明显的生长抑制作用,并可能通过透导肿瘤细胞坏死,从而发挥其细胞毒作用。

Preliminary study of mechanisms of sea pyrimidine on human lung adenocarcinoma multidrug-resistant cell A549/T and its parental cells

Objective: To inversigate the mechanisms of sea pyrimidime on human lung adenocarcioma multidrug resistant cell A549/T and its parental cells A549.Methods: Microculturetetrazolium assay(MTT) and optical microscope were applied to observe growth curve,inhibition rate,and cell morphological changes after A549/T and A549 cells treated with sea pyrimidine.Results: Sea pyrimidine could inhibit growth of human lung adenocarcinoma cells A549/T and A549 both in a time and a dose dependent manner at the dose range of 10～200 μg/ml.Compared with A549 cell,A549/T cell was more sensitive in 12～24 h,less sensitive in 48 h,and of no statistical difference in 72 h.Meanwhile,necrosis increasing,cytoplasm vacuole increasing,formation of nucleus fragments were observed both in A549/T and A549 cells by optical microscope.Conclusion: The growth inhibition and anticancer effects of Sea pyrimidine may be due to its ability to induce tumor tumor cells necrosis.