Effects of the combination of hyperbaric oxygen and 5-fluorouracil on proliferation and metastasis of human nasopharyngeal carcinoma CNE-2Z cells

Undersea Hyperb Med. May-Jun 2010;37(3):141-50.

Abstract

Objective: We investigated the effects of hyperbaric oxygen (HBO2) and/or 5-fluorouracil (5-FU) on the proliferation and metastasis of human nasopharyngeal carcinoma (NPC) cell line CNE2Z and the underlying mechanisms involved.

Methods: Nasopharyngeal carcinoma (NPC) CNE2Z cells were randomly divided into four groups: Group A: control group; Group B: 5-FU group; Group C: HBO2 group; Group D: 5-FU plus HBO2 group. The inhibitory effects on CNE2Z cells proliferation in the four groups after 24, 48 and 72 hours of treatment were measured by MTT-colorimetric method. Transwell chamber assay was performed to determine the effects of HBO2 and/or 5-FU on the metastasis of CNE2Z cells; Expressions of MMP-9 and VEGF in CNE2Z cells were detected by immunocytochemical staining.

Result: A significant difference was observed in the inhibitory effects on CNE2Z cell proliferation (OD values) between the 5-FU group (Group B) and the control group (Group A) after 24, 48, and 72 hours of treatment (p<0.01); between the HBO2 group (group C) and the control group (Group A) after 48 and 72 hours of treatment (p<0.01); and between the HBO2 plus 5-FU group (Group D) and the control group (Group A) as well as the HBO2 plus 5-FU group (Group D) and the HBO2 group (Group C) after 24, 48, and 72 hours of treatment (p<0.01). But a significant difference between the HBO2 plus 5-FU group (Group D) and the 5-FU group (Group B) was observed only after 48 hours of treatment (p=0.030). As for metastasis, as well as MMP-9 and VEGF expression OD values, significant difference was observed between the 5-FU group (Group B) and the control group (Group A) with p<0.05, but not between the HBO2 group (Group C) and the control group (Group A). Although effects on metastasis as well as MMP-9 and VEGF expression OD values were significantly different between the 5-FU plus HBO group (group D) and group A (p<0.01), no difference was observed between Group D and Group B as well as Group D and Group C.

Conclusions: Simple HBO2 treatment after 48 and 72 hours could inhibit the proliferation of nasopharyngeal carcinoma CNE2Z cells. The combination of HBO2 with 5-FU exhibited significant synergism in the suppression of NE2Z cell proliferation only after 48 hours of treatment compared to 5-FU. Simple HBO2 treatment could not reduce the high expressions of MMP-9 and VEGF and inhibit the metastasis of human NPC CNE2Z cells, and no synergistic effect was observed for the combination of HBO2 with 5-FU compared to 5-FU alone.

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Cell Line, Tumor
  • Cell Migration Assays / methods
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Combined Modality Therapy / methods
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use*
  • Humans
  • Hyperbaric Oxygenation*
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase 9 / metabolism
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy*
  • Neoplasm Invasiveness
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antimetabolites, Antineoplastic
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9
  • Fluorouracil