Effect Of Salinomycin On The Proliferation And Apoptosis Of Human Oral Squamous Cell Carcinoma Cells

Objectives: Oral cancer is a common malignant tumor.According to reports,more than 300,000 cases of oral cancer diagnosed in one year,which accounted for 2.1% of the world,and more than 90% of oral cancer are oral squamous cell carcinoma(OSCC),which accounts 1–2% of all human malignant tumors.In China,the incidence of oral squamous cell carcinoma is 1.5%-5.6% of the total incidence of malignant tumors Although the surgical treatment combined with postoperative radiotherapy and/or chemotherapy have achieved exciting success,but the five-year survival was only 55% because of recurrence and metastases.Moreover,the destroy to the patients' faces caused by surgery significantly decreased the quality of social life of patients.Therefore,clinicians and researchers are urgent to find the effective anticancer agents to improve the survival rate and quality of life of patients with oral malignant tumors and reduce side effects.This study was aimed to investigate the effects of salinomycin on the proliferation,apoptosis and angiogenesis of oral squamous carcinoma cells(OSCC)and to further understand the mechanisms of these effects.Methods: The human oral squamous carcinoma cell line CAL-27 was cultured in 0,1,2,4,8,16 and 32?mol/L salinomycin and 0,1.25,2.5,5,10,20,40 and 80?mol/L cisplatin.After co-culture with salinomycin or cisplatin for 24 hours and 48 hours,the proliferation of CAL-27 were detected by CCK-8 assay.After exposed to 0,2,4,8?mol/L salinomycin and 0,5,10,20?mol/L cisplatin for 48 hours,the cell cycle of CAL-27 was detected by flow cytometry assay.Western Blot analysis was performed to analyze the expression of Caspase-3,Caspase-9,PARP,Akt and p-Akt protein in CAL-27.The tube formation was used to detect the effects of salinomycin on the number and length of tubes in human umbilical vein endothelial cells.Results: Both salinomycin and cisplatin significantly inhibited the proliferation of oral squamous cell carcinoma CAL-27 cells in a time-and dose-dependent manner.However,salinomycin showed stronger antiproliferation activity in CAL-27 cells than the first-line chemotherapeutic drug cisplatin.Compared with the control group,CAL-27 cells exhibited markedly higher proportion in G0/G1 phases,and had a significantly lower proportion in S phases and G2/M phases;Cisplatin didn't show cell-cycle specific effect on CAL-27.Salinomycin could up-regulate the expression of Caspase-3 and Caspase-9 in oral squamous cell carcinoma CAL-27 cells.At the same time,the level of PARP,Akt and p-Akt protein were downregulated.Tube formation showed salinomycin inhibited the number of tubes and the length of tube structure of human umbilical vein endothelial cells in a dose-dependent manner.Conclusions: Compared with cisplatin,salinomycin has a better inhibitory effect on the proliferation of CAL-27 and blocks the cell cycle process at the G0/G1 phase.At the same time,salinomycin could trigger apoptosis of OSCC and the mechanism is associated with the Akt/p-Akt signaling pathway.In addition,salinomycin can inhibit angiogenesis in vitro.Salinomycin could be an effect approach to treat OSCC.