摘要
目的探讨顺铂(DDP)联合索拉非尼对三阴性乳腺癌(TNBC)细胞的抑制作用及其可能的分子机制。方法单独及联合给药后采用MTT法测定多种TNBC细胞的增殖,采用Western blot观察MAPK通路关键蛋白的表达情况。结果 MTT法检测发现DDP单药和索拉非尼单药在体外对TNBC细胞株MDA-MB-231、MDA-MB-468、CAL-51增殖都有一定的抑制作用。其中MDA-MB-468和CAL-51细胞对DDP更为敏感。通过中效原理,证实DDP和索拉非尼联合应用时,在各个细胞株中均为协同效应。DDP联合索拉非尼对各细胞株协同抑制的分子机制主要是通过影响MAPK通路关键蛋白的表达实现的,Western blot检测显示各细胞株均表现为p-ERK蛋白表达水平不同程度的下降以及p-JNK蛋白表达水平不同程度的升高。结论 DDP联合索拉非尼在体外能协同抑制多种TNBC细胞株的增殖。
Objective To explore the inhibitory effects of cisplatin （DDP） combined with Sorafenib on triple - nega- tive breast cancer cells （TNBC） in vitro and to discuss the possible mechanisms. Methods Sorafenib and cisplatin were used in single agent or in combination against TNBC cell lines MDA -MB -231, MDA -MB -468 and CAL- 51 in vitro. The inhibitory effects of cisplatin and/or Sorafenib on proliferation of these three cell lines were determined by MTr assay 48h after the applica- tion of the drugs on cell lines. Western blot was used to detect the expression level of key proteins in MAPK pathway. Results Theresults of MTY showed that Sorafenib or DDP alone had certain inhibitory effects on these three cell lines proliferation in vitro. MDA- MB-468 and CAL- 51TNBC cell lines were more sensitive to DDP. Based on the median -effect principle, Sor- afenib combined with DDP showed a synergistic inhibitory effect on the three cell lines proliferation. The molecular mechanism of synergistic inhibitory effect by DDP combined with Sorafenib on each cell line was through affecting key proteins of MAPK path- way. Western blot analysis indicated that p - ERK protein expression levels were decreased, but p - JNK protein expression levels were elevated with different degrees in three cell lines. Conclusion Combined application of cisplatin and Sorafenib may syner- gistically inhibit the proliferation of TNBC cell lines.
出处
《中国全科医学》
CAS
CSCD
北大核心
2012年第18期2042-2045,共4页
Chinese General Practice
关键词
乳腺肿瘤
顺铂
索拉非尼
Breast neoplasms
Cisplatin
Sorafenib
