Inhibitory Effects of Cisplatin Combined with Sorafenib on Triple-Negative Breast Cancer Cells in Vitro

Objective To explore the inhibitory effects of cisplatin(DDP) combined with Sorafenib on triple-negative 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 MTT assay 48h after the application of the drugs on cell lines.Western blot was used to detect the expression level of key proteins in MAPK pathway.Results The results of MTT 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,Sorafenib 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 pathway.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 synergistically inhibit the proliferation of TNBC cell lines.