Nimotuzuma restrains proliferation and induces apoptosis in human osteosarcoma cells by regulation of EGFR/PI3K/AKT signal pathway. Issue 11 (18th April 2019) - Liu, Meihan
Abstract: Osteosarcoma (OS) is a conversant malignant bone tumor, commonly occurs in children and adolescents. Nimotuzuma is an epidermal growth factor receptor (EGRF) monoclonal antibody agent, which has been exploited in varied solid tumors. Nevertheless, the functions of Nimotuzuma in OS remain blurry. We attempted to disclose the impacts of Nimotuzuma on OS cells proliferation and apoptosis. OS MG‐63 and U2OS cells were stimulated with the disparate doses of Nimotuzuma. Then, cell viability, cell cycle, and apoptosis were appraised through executing CCK‐8 and flow cytometry assays. Moreover, the change of mitochondrial membrane potential (ΔΨm) was estimated via JC‐1 fluorescent probe to further probe the impacts of Nimotuzuma on cell apoptosis. The proteins of cell apoptosis, cell cycle, and EGFR/PI3K/AKT were appraised via western blot. Eventually, Nimotuzuma together EGRF or PI3K inhibitor (LY294002) were utilized to dispose MG‐63 to further uncover the latent mechanism. We found that Nimotuzuma remarkably repressed cell viability at a time‐ and dose‐dependent manners in MG‐63 and U2OS cells. The percentage of the S phase cells was evidently reduced by Nimotuzuma through regulating P21, Cyclin E1, and Cyclin D1. In addition, Nimotuzuma obviously evoked cell apoptosis, meanwhile elevated Bid, Bax, and cleaved‐caspase‐3. Further exploration showed that Nimotuzuma decreased ΔΨm in a dose‐dependent manner in MG‐63 and U2OS cells. Besides, we discovered the repressive functions of Nimotuzuma in OS cells proliferation and apoptosis via hindering the EGFR/PI3K/AKT pathway. These investigations testified that Nimotuzuma repressed cell growth by restraining the EGFR/PI3K/AKT pathway in OS cells, hinting the antitumor activity of Nimotuzuma in OS. Abstract : The investigations testified that Nimotuzuma repressed cell growth by restraining the EGFR/PI3K/AKT pathway in osteosarcoma (OS) cells, hinting the antitumor activity of Nimotuzuma in OS