摘要
为研究人类乳腺癌细胞抗药性和突变率的差异及产生机理，作者检测了同来源于ＭＤＡ－ＭＢ－４３５的人类乳腺癌细胞Ｌ－２和Ｂｒ－１的突变率和对药物ＰＡＬＡ的敏感性，并用流式细胞仪测定两细胞株经ＰＡＬＡ处理后细胞周期分布的变化，用ＤＮＡ碎片法研究细胞凋亡，及用ＷｅｓｔｅｒｎＢｌｏｔ测定Ｐ５３蛋白的表达。结果显示：Ｌ－２和Ｂｒ－１细胞的突变率和对ＰＡＬＡ的敏感性存在巨大差异；经ＰＡＬＡ处理后，两细胞株皆表现出细胞周期滞留在Ｓ期，但Ｌ－２细胞开始出现细胞凋亡而Ｂｒ－１细胞仍能存活。在去除培养液中的ＰＡＬＡ后，Ｂｒ－１细胞能恢复正常细胞周期和生长，而Ｌ－２细胞则一直停留在Ｓ期并继续细胞凋亡；在ＰＡＬＡ处理两细胞的过程中都未检测到Ｐ５３蛋白表达的变化。以上结果表明，一种非ｐ５３依赖型的细胞周期Ｓ期滞留启动的细胞凋亡机理，是造成Ｌ－２和Ｂｒ－１乳腺癌细胞抗药性和突变率差异的原因。
To find out different abilities of drug resistance and mutation rate and its fundamental mechanism among the human breast cancer cells, two variants,L2 and Br1, derived from a common parent cell line of MDAMB435, were assayed for sensitivity to PALA and determined for their mutation rate to drug resistance by clone formation and fluctuation analysis respectively.Further, by means of cell growth rate test, flow cytometry, measurement of DNA fragmentation and western blot, the relatioship between drug resistance and mutation rate and cell cycle control and apoptosis was explored. The results showed that the mechanism of Sphase arrest associated appoptosis created such a different ability of drug resistance and stability of genome in two cell lines with identical p53 mutation.
出处
《华西医科大学学报》
CAS
CSCD
1999年第2期142-145,共4页
Journal of West China University of Medical Sciences
