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高压氧与5-氟尿嘧啶联合应用对人鼻咽癌CNE-2Z细胞增殖和转移的影响

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

作者信息

Peng Zheng-Rong, Zhong Wei-Hong, Liu Juan, Xiao Ping-Tian

机构信息

Department of Hyperbaric Oxygen, Xiangya Hospital of Central South University, Changsha, Hunan Province, China.

出版信息

Undersea Hyperb Med. 2010 May-Jun;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.

摘要

目的

我们研究了高压氧(HBO2)和/或5-氟尿嘧啶(5-FU)对人鼻咽癌(NPC)细胞系CNE2Z增殖和转移的影响及其潜在机制。

方法

将鼻咽癌(NPC)CNE2Z细胞随机分为四组:A组:对照组;B组:5-FU组;C组:HBO2组;D组:5-FU加HBO2组。采用MTT比色法检测四组处理24、48和72小时后对CNE2Z细胞增殖的抑制作用。进行Transwell小室实验以确定HBO2和/或5-FU对CNE2Z细胞转移的影响;通过免疫细胞化学染色检测CNE2Z细胞中MMP-9和VEGF的表达。

结果

处理24、48和72小时后,5-FU组(B组)与对照组(A组)对CNE2Z细胞增殖的抑制作用(OD值)有显著差异(p<0.01);处理48和72小时后,HBO2组(C组)与对照组(A组)有显著差异(p<0.01);处理24、48和72小时后,HBO2加5-FU组(D组)与对照组(A组)以及HBO2加5-FU组(D组)与HBO2组(C组)均有显著差异(p<0.01)。但仅在处理48小时后,HBO2加5-FU组(D组)与5-FU组(B组)有显著差异(p = 0.030)。至于转移以及MMP-9和VEGF表达OD值,5-FU组(B组)与对照组(A组)有显著差异,p<0.05,但HBO2组(C组)与对照组(A组)无显著差异。虽然5-FU加HBO组(D组)与A组在转移以及MMP-9和VEGF表达OD值方面有显著差异(p<0.01),但D组与B组以及D组与C组之间无差异。

结论

48和72小时后的单纯HBO2处理可抑制鼻咽癌CNE2Z细胞的增殖。与5-FU相比,HBO2与5-FU联合仅在处理48小时后对NE2Z细胞增殖的抑制表现出显著协同作用。单纯HBO2处理不能降低MMP-9和VEGF的高表达,也不能抑制人NPC CNE2Z细胞转移,且与单独使用5-FU相比,HBO2与5-FU联合未观察到协同作用。

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