Doxorubicin and SN-38 inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest

Abstract

Osteosarcoma is the most common highly malignant primary bone tumor in adolescents and it has a poor prognosis. The aim of the present study was to explore potential chemotherapy drugs for osteosarcoma, in order to provide a theoretical basis for the clinical treatment of the disease. Senescence-associated β-galactosidase (SA-β-gal) staining was used to detect the senescence of drug-treated cells. Bromodeoxyuridine(BRDU) and other methods were used to detect cell proliferation. Immunoprecipitation, immunofluorescence and other techniques were used to explore the impact of drug treatment on the cell cycle. In the present study, doxorubicin (Dox) and 7-ethyl-10-hydroxycamptothecin (SN-38) were found to induce osteosarcoma cell senescence, and senescent cells exhibit the senescence-associated heterochromatin foci phenomenon (SAHF). Cell senescence is induced in osteosarcoma by Dox and SN-38 through inhibiting the expression of the cell cycle-related genes cyclin-dependent kinase (CDK)4, cyclin D1, CDK2 and cyclin E, and inhibit the formation of cell cycle-dependent complexes CDK4/cyclin D1 and CDK2/cyclin E. Eventually, Dox and SN-38 cause cell cycle arrest and induce cell senescence.