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Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (5): 902-906. doi: 10.19723/j.issn.1671-167X.2020.05.018

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Effects of salinomycin on proliferation and apoptosis of oral squamous cell carcinoma

Lei-zhen SU1,2,3,Jie CHEN1,2,Xian LI1,3,Ping JI1,3,∆()   

  1. 1. Department of Oral and Maxillofacial Surgery,Stomatological Hospital of Chongqing Medical University, Chongqing 401120, China
    2. Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401120, China
    3. Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401120, China
  • Received:2018-09-18 Online:2020-10-18 Published:2020-10-15
  • Contact: Ping JI E-mail:jiping_62@hotmail.com
  • Supported by:
    Medical Research Project of Chongqing Health and Family Planning Commission of Chongqing Province(2017MSXM075);Program for Yuzhong District Scientific and Technological Project(20170407);Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education(CXTDG201602006);Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016

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Abstract:

Objective: To investigate the effects of salinomycin on the proliferation and apoptosis of oral squamous carcinoma cells and to further understand the mechanisms of these effects. Methods: The human oral squamous carcinoma cell line CAL-27 was cultured in different concentrations of salinomycin and cisplatin. After co-culture with 0, 1, 2, 4, 8, 16 and 32 μmol/L salinomycin or 0, 1.25, 2.5, 5, 10, 20, 40 and 80 μmol/L cisplatin for 24 hours and 48 hours, the proliferation of oral squamous carcinoma cells were detected by cell counting kit-8(CCK-8) assay. After being exposed to 0, 2, 4, 8 μmol/L salinomycin and 0, 5, 10, 20 μmol/L cisplatin for 48 hours, the cell cycle of oral squamous carcinoma cells was detected by flow cytometry assay, and Western blot analysis was performed to analyze the expressions of cysteine-containing aspartate-specific proteases-3(Caspase-3), cysteine-containing aspartate-specific proteases-9(Caspase-9), poly ADP-ribose polymerase (PARP), protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt) protein in oral squamous carcinoma 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, compared with the first-line chemotherapeutic drug cisplatin, salinomycin showed stronger anti-proliferation activity in oral squamous carcinoma cells than cisp-latin (P<0.001). After being exposed to 8 μmol/L salinomycin, CAL-27 cells exhibited markedly higher proportion in quiescent/ first gap phases (40.40%±1.99% vs. 64.46%±0.90%, P<0.05), and had a significantly lower proportion in synthesis phases and second gap / mitosis phases (24.32%±2.30% vs. 18.73%±0.61%, P<0.05; 35.01%±1.24% vs. 16.54%±1.31%, P<0.05) compared with the dimethyl sulfoxide control group; moreover cisplatin didn’t show cell-cycle specific effect on CAL-27. Western blot proved that salinomycin could up-regulate the expressions of Caspase-3 and Caspase-9 protein in oral squamous cell carcinoma CAL-27 cells (P<0.05). At the same time, the levels of PARP, Akt and p-Akt protein were down-regulated (P<0.05). Conclusion: Compared with cisplatin, salinomycin has a better inhibitory effect on the proliferation of oral squamous carcinoma cells and blocks the cell cycle process at the quiescent / first gap phase. At the same time, salinomycin could trigger apoptosis of oral squamous carcinoma cells and the mechanism is associated with the Akt/p-Akt signaling pathway.

Key words: Salinomycin, Oral squamous cell carcinoma, Cell cycle arrest, Apoptosis

CLC Number: 

  • R739.8

Figure 1

The anti-proliferation effects of salinomycin (A) and cisplatin (B) on CAL-27 cell lines"

Figure 2

Effect of salinomycin and cisplatin on CAL-27 cell cycle After exposed to 0, 2, 4, 8 μmol/L salinomycin(A) and 0, 5, 10, 20 μmol/L cisplatin(B) for 48 hours, the cell cycle of CAL-27 was detected by flow cytometry assay. "

Figure 3

Effect of salinomycin on the apoptosis and the signaling pathway of apoptosis on CAL-27 cell lines A, The expression of Caspase-3, Caspase-9, PARP, Akt and p-Akt protein were detected by Western blot after exposed salinomycin for 48 hours; B, The relative expression of Caspase-3 protein; C, Caspase-9 protein; D, PARP protein; E, Akt protein; F, p-Akt protein; * P < 0.05, vs. control group. PARP, poly ADP-ribose polymerase; Akt, protein kinase B. "

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