Abstract
Berberine (BBR) has been reported to have potent anticancer activity and can increase the anticancer effects of chemotherapy drugs. The present study aims to investigate whether BBR and cisplatin (DDP) exert synergistic effects on the osteosarcoma (OS) MG-63 cell line. In the present study, MG-63 cells were treated with BBR and DDP alone or in combination. The effects of these therapeutics on cell viability, colony formation, migration, invasion, nuclear morphology, apoptosis, and the cell cycle, as well as their role in regulating the expression of proteins related to apoptosis, the cell cycle, and the mitogen-activated protein kinase (MAPK) pathway, were determined. The results demonstrated that BBR or DDP significantly inhibited the proliferation of MG-63 cells in a dose- and time-dependent manner. The combination treatment of BBR and DDP exerted a prominent inhibitory effect on proliferation and colony formation. Furthermore, the results showed that the combination treatment of BBR and DDP enhanced the inhibition of cell migration and invasion and reversed the changes in nuclear morphology. The results showed that the combination treatment of BBR and DDP induced apoptosis and cell cycle arrest in the G0/G1 phase. Mechanistically, the combination treatment of BBR and DDP inhibited the expression of MMP-2/9, Bcl-2, CyclinD1, and CDK4, enhanced the expression of Bax and regulated the activity of the MAPK pathway. Collectively, our data suggest that the combination therapy of BBR and DDP markedly enhanced OS cell death.
Highlights
Accepted: 12 March 2021Osteosarcoma (OS) is a common malignant tumor that originates from the stroma of osteogenic material [1]
The results showed that BBR or DDP exhiba time- and dose-dependent inhibitory effect on MG-63 cells (Figure 1A,B)
Our study showed that DDP had cytotoxicity on HBMSC cells, the IC50 value of DDP for HBMSC cells was 236.60 μM for mild cytotoxicity cells, 1C)
Summary
Accepted: 12 March 2021Osteosarcoma (OS) is a common malignant tumor that originates from the stroma of osteogenic material [1]. Treatment usually includes neoadjuvant chemotherapy, surgical resection, and a successive course of chemotherapy following surgery [3]. Prognosis has improved for patients with localized disease, patients with metastatic disease still have a poor prognosis [4]. Patients with metastatic disease at diagnosis or with recurrent disease have a five-year survival rate of only 20% [5]. Cisplatin (DDP), a first-line chemotherapeutic drug, is widely used to treat various tumors, including bladder cancer, cervical cancer, small cell lung cancer, and gastric cancer [6]. A higher cumulative dose and higher doses per treatment of DDP result in greater irreversible kidney injury [10,11,12]
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