引用本文:张 政,翁敬锦,韦海明,兰桂萍,覃 颖,覃扬达,孙金杰,司勇锋.晚期鼻咽癌患者基因治疗前后TS和GST-π及TopoⅡ的表达变化及其与预后的关系[J].中国临床新医学,2012,5(12):1126-1130.
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晚期鼻咽癌患者基因治疗前后TS和GST-π及TopoⅡ的表达变化及其与预后的关系
张 政,翁敬锦,韦海明,兰桂萍,覃 颖,覃扬达,孙金杰,司勇锋
530021 南宁,广西壮族自治区人民医院耳鼻咽喉头颈肿瘤科(张 政,翁敬锦,兰桂萍,覃 颖,覃扬达,孙金杰,司勇锋),病理科(韦海明)
摘要:
[摘要] 目的 初步探讨重组人p53腺病毒(rAd-p53)鼻咽部瘤内注射前后的鼻咽癌原发灶中胸苷酸合成酶(TS)、谷胱甘肽S-转移酶π(GST-π)和拓扑异构酶Ⅱ(TopoⅡ)的表达变化及其临床意义。方法 采用免疫组化法检测80例晚期鼻咽癌患者治疗前后肿瘤组织中TS、GST-π和TopoⅡ的表达情况。结果 常规放化疗组在治疗后其TS、GST-π和TopoⅡ的表达明显升高(P分别为0.01、0.01、0.00),基因治疗组和单纯放疗组其治疗后TS、GST-π和TopoⅡ的表达未见明显改变(P>0.05)。三组间的复发率和转移率差异无统计学意义(P=0.95)。疗前GST-π阴性患者其复发率和转移率明显低于阳性患者(8.93% vs 54.17%,P=0.00)。结论 GST- π蛋白的异常表达与晚期鼻咽癌治疗后复发转移有关。基因治疗晚期鼻咽癌可能通过抑制TS、GST-π、TopoⅡ蛋白表达进而逆转鼻咽癌化疗耐药。
关键词:  p53基因治疗  化疗耐药  TS  GST-π  TopoⅡ
DOI:10.3969/j.issn.1674-3806.2012.12.09
分类号:R 739.63
基金项目:广西卫生厅重点科研课题(编号:重200721)
The expression of TS, GST-π, TopoⅡ in advanced nasopharyngeal carcinoma patients treated with gene therapy and its influence on prognosis
ZHANG Zheng, WENG Jing-jin, WEI Hai-ming, et al.
Department of Otolaryngology Head and Neck Oncology, the People′s Hospital Guangxi Zhuang Autonomous Region, Nanning 530021,China
Abstract:
[Abstract] Objective To investigate the expression of thymidylate synthase (TS), glutathione S-transferase enzyme π(GST-π) and topoisomerase Ⅱ (Topo Ⅱ) protein before and after the recombinant human p53 adenovirus (rAd-p53) intratumoral injection and its significance.Methods Eighty patients with advanced nasopharyngeal carcinoma were randomly divided into 3 groups:the gene therapy group (30 cases): rAd-p53 intratumoral injection and concurrent chemo-radiotherapy, the conventional chemoradiotherapy group (30 cases) and the radiotherapy group (20 cases). Clinical data and the nasopharyngeal tumor tissues which were intratumoral injection with rAd-p53 were collected. The two-step immunohistochemical was done to detect the TS, GST- π and TopoⅡ protein expression in the primary tumor tissue of nasopharyngeal carcinoma.Results The expression TS, GST-π and Topo Ⅱ in conventional chemoradiotherapy group was significantly higher than that before treatment (P values were 0.01,0.01,0.00). In gene treatment group, the expression TS, GST-π and Topo Ⅱdid not change significantly (P>0.05).There were no significant difference in the expression of TS, GST-π and Topo Ⅱbefore and after radiotherapy alone(P>0.05). Among the three groups, the recurrence rate and metastasis rate were not significantly different (P = 0.95). The recurrence rate in GST-π negative patients was significantly lower than that in positive patients (8.93% vs. 54.17%, P = 0.00).Conclusion GST-π protein expression is positively correlated with recurrence and metastasis in patients with advanced nasopharyngeal carcinoma after treatment.The rAd-p53 intratumoral injection can reverse chemo-resistance of nasopharyngeal carcinoma by inhibition of GST-π, Topo Ⅱ protein, which might be its mechanism of NPC treatment.
Key words:  p53 gene therapy  Resistance to chemotherapy  TS  GST-π  Topo Ⅱ