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目的 :研究丝裂原活化蛋白激酶/细胞外信号调节激酶(mitogen-activated protein kinase/extracellular signal-regulated kinase,MAPK/ERK)通路抑制剂PD98059对卵巢癌SKOV3和OVCAR3细胞增殖及侵袭能力的影响,初步探讨阻断MAPK/ERK信号转导通路以治疗卵巢癌的可能性。方法:体外培养人上皮性卵巢癌SKOV3和OVCAR3细胞,然后用不同浓度的PD98059处理细胞不同时间。采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)检测2种细胞的增殖活性。蛋白质印迹法检测PD98059对2种细胞中磷酸化ERK(phospho-ERK,p-ERK)蛋白表达的影响。Transwell小室法检测PD98059作用后SKOV3和OVCAR3细胞侵袭能力的变化。结果:PD98059在一定浓度范围内能够明显抑制卵巢癌细胞SKOV3和OVCAR3的增殖,其作用具有时间及浓度依赖性(P值均<0.05)。PD98059能够抑制ERK1/2的磷酸化,即下调p-ERK1/2蛋白的表达(P<0.05),从而使得ERK1/2信号转导途径失活。同时,PD98059在一定浓度范围内能抑制2种卵巢癌细胞的侵袭能力(P值均<0.05)。结论:PD98059可能通过阻断ERK1/2信号通路,抑制人上皮性卵巢癌SKOV3和OVCAR3细胞的增殖和侵袭能力。
Objective: To investigate the effect of PD98059, a mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK / ERK) pathway inhibitor, on the proliferation and invasion of ovarian cancer SKOV3 and OVCAR3 cells. To explore the possibility of blocking the MAPK / ERK signal transduction pathways to treat ovarian cancer. Methods: Human ovarian epithelial ovarian cancer SKOV3 and OVCAR3 cells were cultured in vitro, then treated with different concentrations of PD98059 for different time. Cell proliferation kit-8 (cell counting kit-8, CCK-8) was used to detect the proliferative activity of the two kinds of cells. The effect of PD98059 on the expression of phospho-ERK (p-ERK) protein in two kinds of cells was detected by Western blotting. Transwell chamber assay PD98059 changes in SKOV3 and OVCAR3 cell invasive ability. Results: PD98059 could obviously inhibit the proliferation of ovarian cancer cells SKOV3 and OVCAR3 in a certain concentration range. The effect of PD98059 was time-dependent and concentration-dependent (P <0.05). PD98059 could inhibit the phosphorylation of ERK1 / 2, that is down-regulate the expression of p-ERK1 / 2 (P <0.05), thus inactivating the ERK1 / 2 signal transduction pathway. At the same time, PD98059 could inhibit the invasion ability of two kinds of ovarian cancer cells in a certain concentration range (P <0.05). Conclusion: PD98059 may inhibit the proliferation and invasion of human epithelial ovarian cancer SKOV3 and OVCAR3 cells by blocking the ERK1 / 2 signaling pathway.