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Objective To investigate the molecular mechanism of HK2 on promoting cell proliferation and migration through p-ERK1/2 in cervical cancer cell line HeLa. Methods Expression of HK2 in cervical cancer cell lines was detected by Western blot and immunocychemistry. Over-expressed HK2 cell line(HeLa-HK2) was established by using G418. Wound-healing and Transwell cells assays were used to detect the migratory and invasive potential in HeLa-HK2 and in control cell lines. Cell growth curves, MTT assay and flow cytometry were used to detect cell proliferation, cell viability and cell cycle. The expression of ERK1/2, p-ERK1/2, cyclin A and Slug was detected by using Western blot and immunocytochemistry. The ERK inhibitor (FR180204) was used to inhibit expression of ERK1/2 and p-ERK1/2, and the potential of cell proliferation, migration and invasion was observed in these cells. Results HeLa-HK2 cells that stably expressing HK2 was successfully constructed. HK2 enhanced cell migration, invasion and growth potential in HeLa cells. The expression of ERK1/2, p-ERK1/2, cyclin A and Slug was higher in HeLa-HK2 cells than those in control cells. The protein level of ERK1/2, p-ERK1/2, cyclin A and Slug was decreased in FR180204 treated HeLa-HK2 cells, and the potential of growth, migratory and invasive were also attenuated by FR180204 in HeLa-HK2 cells. Conclusions HK2 promotes cell growth, migration and invasion in HeLa cells by up-regulating expression of cyclin A and Slug through stimulating p-ERK1/2.