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

Hong-Bin Sun; He-Yuan Wang; Bing Wu; Zhong-Feng Wang; Li-Zhe Wang; Fu-Qiang Li; Jun-Duo Wu; Le-Ning Zhang

doi:10.3892/ol.2019.11019

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

Oncol Lett. 2019 Dec;18(6):6385-6396. doi: 10.3892/ol.2019.11019. Epub 2019 Oct 29.

Authors

Hong-Bin Sun¹, He-Yuan Wang², Bing Wu³, Zhong-Feng Wang⁴, Li-Zhe Wang⁵, Fu-Qiang Li⁶, Jun-Duo Wu⁷, Le-Ning Zhang¹

Affiliations

¹ Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
² Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
³ Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
⁴ Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
⁵ Department of Pediatric Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
⁶ Eye Center of The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
⁷ Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

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.

Keywords: BRCA1-p53 pathway; MG-63 cell line; cisplatin; combined cisplatin-radiation; osteosarcoma; radiation.