Abstract:
Objective To provide a possible mechanism underlying oncostatin M (OSM)-induced tumor growth by investigating the effects on growth of liver cancer cells and its molecular pathway.
Methods Cell growth rates were analyzed after OSM treatment in human liver cancer cell lines-SMMC-7721 and HepG2. Cellular senescence based on growth arrest and morphologic phenotype of cells was detected by senescence-associated β-galactosidase (SA-β-gal) staining. Cell cycle profile was examined by flow cytometry. The expression of key regulators of cell proliferation including cyclin-dependent kinase inhibitors (p16, p21, and p27) and c-Myc were analyzed at the level of mRNA and protein.
Results OSM suppressed cell proliferation in a dose-dependent manner. Upon drug treatment, morphological changes of cells notably implicated a senescent phenotype, which was further supported by the positive SA-β-gal staining. Meanwhile, OSM induced an increased proportion of cells at G0/G1 phase, which corresponded to the elevated expression of p21 and p27 at mRNA and protein levels. Unexpectedly, oncogene c-Myc was also dramatically upregulated upon OSM treatment.
Conclusion As a key regulator of cell proliferation and survival, c-Myc can be upregulated though the OSM-activated STAT3 pathway. While in short term, such hyperactive oncogene would induce cellular senescence as a barrier to transformation in cells with intact p53 machinery. These findings suggest that the elevated OSM during the earliest stages of liver cancer might serve as a tumor suppressor.
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