The Role And Mechanism Of Oncostatin M In Ovarian Cancer Cells In Vitro

purpose The purpose of this study was to investigate the possible role of recombinant human OSM (rH-OSM) in human ovarian cancer SKOV3 cells,and if the ERK1/2, p38, STAT3 signaling pathways are involved.Methods The cells were treated with rH-OSM (100 ng/mL) in RPMI-1640 medium with 2% FBS, SKOV3 cells measured in using MTT assays after treatment with different concentrations rH-OSM in different times; SKOV3 cells treated with rH-OSM analyze by Hoechst 33342/PI staining and AO/EB staining in order to show if proliferation of SKOV3 cells induce by rH-OSM; p-ERK1/2,p-p38, p-STAT3 protein expression in treated SKOV3 cells analyse by western blot. And then we investigated whether rH-OSM-induced change is mediated by activation of p-ERK1/2, p-p38, p-STAT3 in ovarian cancer cell line SKOV3. The MEK inhibitor U0126 was used, and found to specifically block p-ERK activation. An inhibitor of p-p38 kinase, SB202190, was used. SB202190 (50 nmol/mL) was able to specifically block p-p38 activation. So U0126 and SB202190 was utilized to assess the role of p-ERK and p-p38 in rH-OSM induced growth of SKOV3 cells. STAT3 also was silenced by RNAi to assess the role of p-STAT3 in rH-OSM induced growth of SKOV3 cells.Result The study showed that rH-OSM promoted the proliferation of SKOV3 ovarian cancer cells. Western blot analysis showed that p-STAT3, phosphorylated-extracellular regulated protein kinase 1/2(p-ERK1/2), p-p38 protein levels were increased in the cell lines treated with rH-OSM. Proliferation in SKOV3 cells induced by rH-OSM was suppressed by inhibitors of p-p38 or p-ERK 1/2. Western blot analysis showed that p-STAT3 protein was decreased in SKOV3 cells treated by inhibitors of p-p38 prior to treatment with rH-OSM. Also, p-STAT3 was not increased in the cells treated by inhibitors of ERK1/2 prior to treatment with rH-OSM. Cell proliferation showed a moderate increase in sh-STAT3+rh-OSM control group compared with sh-STAT3 group. And after cells treated with rh-OSM, p-ERK1/2 and p-p38 protein expression was similarly affected in sh-STAT3+rh-OSM group compared with SKOV3 cells with STAT3.Conclusion These data demonstrate that rH-OSM promotes the proliferation of SKOV3 ovarian cancer cells and the growth-promoting activity of rH-OSM can be mediated through different signaling pathways. ERK1/2 and p38 proteins regulate STAT3 expression in SKOV3 cells, while STAT3 may be pivotal to the proliferation of SKOV3 cells in vitro.