Anticancer Effect Of Sorafenib Combined With Taxol On A549/Taxol Lung Cancer Cell Line In Vitro And Its Mechanism

Bacground and objectivesMost patients with non-small cell lung cancer(NSCLC)are diagnosed with advanced inoperable disease and only have to choose systemic chemotherapy.But patients always discontinue chemotherapy because of its drug resistance and significant toxicities.Thus it is of great significance for the improvement of patients' survival to seek the combination of chemotherapy and other drugs.One such a drug,paclitaxel(PTX)has become a first-line treatment for NSCLC.Sorafenib,as a small molecular multi-targets inhibitors appoved on clinical use,has been approved single-agent sorafenib could benefits OS in patients with advanced untreated NSCLC.Unfortunately,sorafenib in combination with cytotoxic agents for the treatment of NSCLC patients failed to reach the expected goals in a Phase III study.The aim of this study was to investigate the anticancer effect of sorafenib combined with paclitaxel on A549/Taxol lung cancer cell line in vitro and futher study its possible mechanism,and then provide theoretical basis for the future clinical combination treatment of NSCLC.MethodsThrough the A549/Taxol cell culture,set the blank group,the sorafenib,the PTX,and sorafenib combined PTX group.The cell proliferation and apoptosis of different groups were measured by MTT and flow cytometry,respectively.The expression level of bcl-2 and Ezrin?p-Ezrin were detected by Real-Time PCR and Western Blot.Results1.Determined by MTT cell proliferation experiment,the inhibition of cell growth gradually strengthened with the increase of concentration of single sorafenib and single PTX.Sorafenib combined with taxol markedly inhibited cell proliferation more than other groups.2.Flow cytometry showed that sorafenib combined with taxol dramatically increased the apoptosis of cell.3.Real-Time PCR found that sorafenib,taxol alone inhibited the expression level of bcl-2 compared with the blank control group,and the bcl-2 expression of sorafenib in combination with taxol group significantly lower than other groups.4.Western blot analysis discovered the expression of Ezrin?p-Ezrin are high in blank group.They were reduced in single drug groups and was effectively suppressed in the sorafenib in combination with taxol group.ConclusionsSorafenib combined with taxol have stronger anticancer effect than single drugs,maybe by inhibiting the expression of bcl-2 and Ezrin ?p-Ezrin.