Oral cancer cells sustainedly infected with Porphyromonas gingivalis exhibit resistance to Taxol and have higher metastatic potential

Oncotarget. 2017 Jul 18;8(29):46981-46992. doi: 10.18632/oncotarget.16550.

Abstract

Major obstacles to improving the prognosis of patients with oral squamous cell carcinoma (OSCC) are the acquisition of resistance to chemotherapeutic agents and development of metastases. Recently, inflammatory signals are suggested to be one of the most important factors in modulating chemoresistance and establishing metastatic lesions. In addition, epidemiological studies have demonstrated that periodontitis, the most common chronic inflammatory condition of the oral cavity, is closely associated with oral cancer. However, a correlation between chronic periodontitis and chemoresistance/metastasis has not been well established. Herein, we will present our study on whether sustained infection with Porphyromonas gingivalis, a major pathogen of chronic periodontitis, could modify the response of OSCC cells to chemotherapeutic agents and their metastatic capability in vivo. Tumor xenografts composed of P. gingivalis-infected OSCC cells demonstrated a higher resistance to Taxol through Notch1 activation, as compared with uninfected cells. Furthermore, P. gingivalis-infected OSCC cells formed more metastatic foci in the lung than uninfected cells.

Keywords: Notch1; Porphyromonas gingivalis; Taxol; metastasis; oral cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bacteroidaceae Infections / complications*
  • Bacteroidaceae Infections / metabolism
  • Bacteroidaceae Infections / microbiology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Resistance, Neoplasm*
  • Gene Expression
  • Humans
  • Male
  • Mice
  • Mouth Neoplasms / etiology*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Metastasis
  • Paclitaxel / pharmacology*
  • Porphyromonas gingivalis*
  • Receptor, Notch1 / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Receptor, Notch1
  • Paclitaxel