The inhibitory effects of cisplatin‑radiation combination treatment on malignant osteosarcoma MG‑63 cells and BRCA1‑p53 pathways are more efficient than single treatments

Abstract

The poor prognosis of patients with osteosarcoma remains a persistent problem, in particular for patients with unresectable tumors or metastasis. Therefore, combination of radiotherapy and chemotherapy has been considered for patients with metastasis or recurrence, patients unsuitable for surgery and patients refusing surgery. The present study aimed to investigate the effect of the combined treatment with cisplatin and radiation therapy on the biological characteristics of the osteosarcoma cell line MG-63 and the breast cancer 1 (BRCA1)-associated signaling pathways. Cell proliferation was determined using Cell Counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. Cell migration was examined by Transwell assay. The mRNA and protein expression levels of candidate genes, including BRCA1 and p53, were determined by reverse transcription-quantitative PCR and western blotting, respectively. The results demonstrated that combined treatment with radiation and cisplatin significantly inhibited MG-63 cell proliferation compared with radiation or cisplatin treatment alone. Furthermore, radiation, cisplatin or the combined treatment with radiation and cisplatin increased the apoptosis rate of MG-63 cells, which resulted in G2 phase arrest, and significantly decreased the migratory capacity of MG-63 cells. In addition, the apoptosis rate of MG-63 cells following combined radiation and cisplatin treatment was higher compared with the cisplatin group, but lower compared with the radiation group. Furthermore, combined treatment with radiation and cisplatin decreased the mRNA and protein expression levels of BRCA1 and p53. Additionally, combined treatment with radiation and cisplatin had a more potent inhibitory effect on p53 expression than on BRCA1 expression. In addition, combination of radiation and cisplatin had a higher inhibitory effect on Bax protein level and a higher inductive effect on Bcl-2 protein level compared with treatments with radiation and cisplatin alone. The results demonstrated that combined treatment of radiation and cisplatin exhibited superior therapeutic effects on osteosarcoma MG-63 cells compared with radiation or cisplatin treatment alone, which may be mediated by the BRCA1-p53 signaling pathway.

Effects of Rapamycin Combined with Cisplatin on Tumor Necrosis Factor TNF-α in MG-63 Cells

“…In this study, osteosarcoma MG-63 cells were divided into four groups, i.e., a control group, a RAPA group, a CDDP group, and a RAPA + CDDP group to detect the expression quantity of TNF. The results of statistical analysis clarified the killing effect of the combination of the two drugs on tumor cells 22 .…”

Long Noncoding RNA NORAD/MiR-26a-5p/NAMPT (Visfatin) Axis Regulates Proliferation and Apoptosis of Human Osteosarcoma Cells

“…The ve-year survival rate is about 50-60% for OS patients, and nearly 40% of these patients succumb to lung metastases (2). At present, the standard strategy for OS patients is a combination of treatments consisting of surgical resection, systemic chemotherapy and restoration of limb function (3). However, anti-metastasis therapy is not yet satisfactory; systemic chemotherapy may lead to severe side effects, and has different degrees of injury on organs of the human body; surgery resection with a large impact on limb function often make it di cult on the patients.…”