Tigecycline exerts an antitumoral effect in oral squamous cell carcinoma

Oral Dis. 2015 Jul;21(5):558-64. doi: 10.1111/odi.12311. Epub 2015 Apr 6.

Abstract

Objective: To explore whether antibacterial drug tigecycline could exert an antitumoral effect in oral squamous cell carcinoma (OSCC).

Materials and methods: Two OSCC cell lines Tca8113 and KB were used in this study. To investigate the cytostatic effects of tigecycline in OSCC, cell growth was tested by trypan blue staining, MTT assay, and Brdu immunofluorescence staining. Then, the apoptosis proportion was measured by FITC Annexin-V and PI labeling, and cell cycle was determined by PI staining. The expression of caspase 3 (CASP3) and cell cycle regulatory protein was detected by Western blot assay. Finally, the clonogenesis and tumorigenesis capacity were analyzed by soft agar growth and xenograft model.

Results: Here, we showed that tigecycline significantly inhibited cell growth and proliferation in OSCC cell lines Tca8113 and KB. It did not induce cell apoptosis but led to an increase of cells in G0/G1 phase with down-regulation of cyclin E2 (CCNE2) and cyclin-dependent kinase4 (CDK4) protein expression. We also showed that tigecycline inhibited colony formation in soft agar and reduced tumor growth in a xenograft model.

Conclusion: Our results suggested that tigecycline might be used as a novel candidate agent for the treatment of OSCC.

Keywords: apoptosis; oral squamous cell carcinoma (OSCC); proliferation; tigecycline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / biosynthesis
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinases / biosynthesis
  • Cyclins / biosynthesis
  • Down-Regulation / drug effects
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Heterografts
  • Humans
  • Mice
  • Mice, SCID
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Squamous Cell Carcinoma of Head and Neck
  • Tigecycline
  • Tumor Stem Cell Assay

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • CCNE2 protein, human
  • Cyclins
  • Tigecycline
  • Cyclin-Dependent Kinases
  • CASP3 protein, human
  • Caspase 3
  • Minocycline