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Article

Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis

  • Authors:
    • Fu-Yao Liu
    • Yan-Hui Wu
    • Shao-Jun Zhou
    • Yue-Ling Deng
    • Zun‑Yi  Zhang
    • Er-Lei Zhang
    • Zhi-Yong Huang
  • View Affiliations / Copyright

    Affiliations: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China, Department of Gastroenterology, Mianyang Center Hospital, Mianyang, Sichuan, P.R. China
  • Pages: 835-844
    |
    Published online on: June 12, 2014
       https://doi.org/10.3892/or.2014.3248
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Abstract

Minocycline, a semisynthetic tetracycline, is a highly lipophilic molecule capable of infiltrating tissues and blood. Previous studies have revealed the functions and mechanisms of minocycline in anti-inflammation, protection of the nervous system and certain tumors. The role of minocycline has never been investigated in hepatocellular carcinoma (HCC). The functions of minocycline on HCC cells were investigated using immunohistochemical staining and western blotting. Minocycline was applied to L02, HepG2 and Huh7 cells, and the growth characteristics were studied. Cisplatin was administered in combination with minocycline in this study. Cell cycle and apoptosis analyses were employed to investigate the mechanisms underlying the growth regulation associated with minocycline and(or) cisplatin. Minocycline caused S phase cell cycle arrest and an increase in the apoptotic rate associated with upregulation of p27, cleaved-caspase8, cleaved-caspase3 and cleaved-PRAP-1. Low dose of cisplatin promoted cell cycle arrest and apoptosis, whereas minocycline was mainly associated with upregulation of cleaved-PARP-1. The combination of cisplatin and minocycline increased the rate and extent of cell cycle arrest and increased the apoptosis rate caused by minocycline. A novel mechanism was revealed. Minocycline functions as an antitumor drug in HCC by regulating p27, caspase-3 and PARP-1. Cisplatin enhanced minocycline's effect on PARP-1.
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Copy and paste a formatted citation
Spandidos Publications style
Liu F, Wu Y, Zhou S, Deng Y, Zhang ZY, Zhang E and Huang Z: Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis. Oncol Rep 32: 835-844, 2014.
APA
Liu, F., Wu, Y., Zhou, S., Deng, Y., Zhang, Z., Zhang, E., & Huang, Z. (2014). Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis. Oncology Reports, 32, 835-844. https://doi.org/10.3892/or.2014.3248
MLA
Liu, F., Wu, Y., Zhou, S., Deng, Y., Zhang, Z., Zhang, E., Huang, Z."Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis". Oncology Reports 32.2 (2014): 835-844.
Chicago
Liu, F., Wu, Y., Zhou, S., Deng, Y., Zhang, Z., Zhang, E., Huang, Z."Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis". Oncology Reports 32, no. 2 (2014): 835-844. https://doi.org/10.3892/or.2014.3248
Copy and paste a formatted citation
x
Spandidos Publications style
Liu F, Wu Y, Zhou S, Deng Y, Zhang ZY, Zhang E and Huang Z: Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis. Oncol Rep 32: 835-844, 2014.
APA
Liu, F., Wu, Y., Zhou, S., Deng, Y., Zhang, Z., Zhang, E., & Huang, Z. (2014). Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis. Oncology Reports, 32, 835-844. https://doi.org/10.3892/or.2014.3248
MLA
Liu, F., Wu, Y., Zhou, S., Deng, Y., Zhang, Z., Zhang, E., Huang, Z."Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis". Oncology Reports 32.2 (2014): 835-844.
Chicago
Liu, F., Wu, Y., Zhou, S., Deng, Y., Zhang, Z., Zhang, E., Huang, Z."Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis". Oncology Reports 32, no. 2 (2014): 835-844. https://doi.org/10.3892/or.2014.3248
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