Abstract:

Objective   To investigate the effects of MEK/ERK inhibitor PD98059, cisplatin and the combined treatment on the proliferation of human ovarian carcinoma cell SKOV3, and to investigate the potential mechanism. Methods   Cell Counting Kit-8（CCK-8）was used to investigate the SKOV3 cell proliferative inhibition rates of different groups: the blank control group, the cisplatin group, the PD98059 group and the combined treatment group. Real-Time PCR was used to detect the expression levels of WW domain-containing Oxidoreductase (WWOX) and extracellular regulated protein kinases (ERK) mRNA. Western blotting analysis was used to measure the expression of phosphorylated ERK1/2(p-ERK1/2) in different groups. The morphological changes of various groups were observed under the light microscope. Flow cytometry was employed to analyze the apoptosis rate of SKOV3 cells in different groups. Results   The inhibitory effect on the proliferation of SKOV3 cells in the combined treatment group was more significant compared with the other three groups (P<0.05). RT-PCR analysis showed that the expressions of WWOX mRNA were increased in the cisplatin group and the combined treatment group compared with the other two groups. The WB analysis showed that the expressions of p-ERK1/2 in the PD98059 group and the combined treatment group were higher compared with the other two groups. More adherent cells were observed in the blank control group and the PD98059 group under the light microscope. There were less adherent cells in the cisplatin group and the combined treatment group, and cytoplasmic dissolution of cells could be observed under the light microscope in these two groups. Conclusion   PD98059 combined with cisplatin exhibited significant inhibitory effect on the proliferation of SKOV3 cells via regulating the expression of WWOX gene and the ERK pathway.

Key words: Ovarian neoplasms； Cisplatin； WW domain-containing; Oxidoreductase； Extracellular Regulated protein Kinases