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


RESULTS
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.
Peng
Zheng-Rong
ZR
Department of Hyperbaric Oxygen, Xiangya Hospital of Central South University, Changsha, Hunan Province, China. pengzr@tom.com
Zhong
Wei-Hong
WH
Liu
Juan
J
Xiao
Ping-Tian
PT
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D054443:Cell Migration Assays / Q000379:methods; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003131:Combined Modality Therapy / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006931:Hyperbaric Oxygenation; D020128:Inhibitory Concentration 50; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009361:Neoplasm Invasiveness; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9; D005472:Fluorouracil