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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. "

[1] Ferlay J, Soerjomataram1 I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015,136(5):E359-E386.
doi: 10.1002/ijc.29210 pmid: 25220842
[2] 孟宪瑞, 刘进忠. 口腔癌的早期诊断[J]. 国际口腔医学杂志, 2008,35(3):329-331.
[3] Abrahão R, Anantharaman D, Gaborieau V, et al. The influence of smoking, age and stage at diagnosis on the survival after larynx,hypopharynx and oral cavity cancers in Europe: The ARCAGE study[J]. Int J Cancer, 2018,143(1):32-44.
doi: 10.1002/ijc.31294 pmid: 29405297
[4] Cho H, Nishiike S, Yamamoto Y, et al. Docetaxel, cisplatin,and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma[J]. Auris Nasus Larynx, 2015,42(5):396-400.
doi: 10.1016/j.anl.2015.02.009 pmid: 25721854
[5] Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening[J]. Cell, 2009,138(4):645-659.
doi: 10.1016/j.cell.2009.06.034 pmid: 19682730
[6] Zhang B, Wang X, Cai F, et al. Effects of salinomycin on human ovarian cancer cell line OV2008 are associated with modulating p38 MAPK[J]. Tumor Biol, 2012,33(6):1855-1862
doi: 10.1007/s13277-012-0445-9
[7] Wu D, Zhang Y, Huang J, et al. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo[J]. Biochem Bioph Res Co, 2014,443(2):712-717.
doi: 10.1016/j.bbrc.2013.12.032
[8] Dhaheri AI, Attoub S, Arafat K, et al. Salinomycin induces apoptosis and senescence in breast cancer: Up regulation of p21, down regulation of survivin and histone H3 and H4 hyperacetylation[J]. BBA-GEN Subjects, 2013,1830(4):3121-3135.
doi: 10.1016/j.bbagen.2013.01.010
[9] Arafat K, Iratni R, Takahashi T, et al. Inhibitory effects of salinomycin on cell survival, colony growth, migration, and invasion of human non-small cell lung cancer A549 and LNM35: Involvement of NAG-1[J]. PLoS One, 2013,8(6):e66931.
doi: 10.1371/journal.pone.0066931 pmid: 23805285
[10] Parajuli B, Lee HG, Kwon SH, et al. Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells[J]. Cancer Epidemiology, 2013,37(4):512-517.
doi: 10.1016/j.canep.2013.02.008
[11] 亓放, 张宝泉, 徐炎, 等. 顺铂诱导的喉癌细胞凋亡及其对细胞周期的影响[J]. 中华医学杂志, 1999,79(4):298-301.
[12] 徐志巧, 庞国明. 实用肿瘤临床药物手册[M]. 北京: 中国医药科技出版社, 2013: 282.
[13] Fuchs D, Heinold A, Opelz G, et al. Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells[J]. Biochem Bioph Res Co, 2009,390(3):743-749.
doi: 10.1016/j.bbrc.2009.10.042
[14] Nuutinen U, Postila V, Matto M, et al. Inhibition of PI3-kinase-Akt pathway enhances dexamethasolle-induced apoptosis in a human follicular lymphoma cell line[J]. Exp Cell Res, 2006,312(3):322-330.
doi: 10.1016/j.yexcr.2005.10.023 pmid: 16309671
[15] Jeong SJ, Dasgupta A, Jung KJ, et al. PI3K/AKT inhibition induces caspase-dependent apoptosis in HTLV-1 transformed cells[J]. Virology, 2008,370(2):264-272.
doi: 10.1016/j.virol.2007.09.003 pmid: 17931677
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