论文标题:mdr-1产物pgp在鼻咽癌组织中放疗前、放疗后表达的初步研究
Preliminary Study of P-Glycoprotein Expression, A Multi-Drug Resistance Gene-1 Product, in Patients with Nasopharyngeal Carcinoma Pre-and Post-Radiotherapy
论文作者 刘宇
论文导师 张幸平,论文学位 硕士,论文专业 影像医学与核医学
论文单位 重庆医科大学,点击次数 73,论文页数 55页File Size3503k
2003-04-01论文网 http://www.lw23.com/lunwen_974681947/ 鼻咽肿瘤/放射疗法,多药耐药性,p-糖蛋白,bcl-2蛋白,p53蛋白,免疫组织化学
nasopharyngeal neoplasms /radiotherapy,multi-drug resistance,p-glycoprotein,p53 protein,bcl-2 protein,immunohistochemistry
目的：①初步探讨放射治疗前、放射治疗后鼻咽癌组织多药耐药基因产物p-糖蛋白的表达及变化特点。②结合凋亡相关基因bcl-2和p53，初步分析这些基因蛋白表达在鼻咽癌发生发展中的作用。材料与方法：选择2001年3月至2002年8月，我科收治且未经放疗、化疗, 经病理证实的鼻咽鳞癌患者64例，采用免疫组织化学SP法，检测了鼻咽癌组织中pgp和bcl-2，p53基因蛋白表达，并对放疗前、放疗后鼻咽部活检均证实为鳞癌的48例96对鼻咽癌组织检测了放疗后的pgp，作相关因素分析。结果：①未经治疗的64例鼻咽鳞癌组织中，pgp和bcl-2，p53基因蛋白表达阳性率分别为17.19%(11/64) 、89.06%（57/64）、76.56%(49/64)，而在10例鼻咽部炎症组织中，上述三种蛋白表达阳性率分别为0%、10%（1/10）、10%（1/10）。bcl-2和p53基因蛋白表达与鼻咽部炎症组织相比，差异有显著意义（P＜0.0001，P＜0.0001）。②放疗后鼻咽癌组织中pgp表达阳性率为75.00%（36/48），放疗后鼻咽癌组织中pgp表达较放疗前有增高趋势，放疗后鼻咽癌组织中pgp阳性表达率与放疗前相比存在显著性差异（P＜0.001）。③pgp和bcl-2，p53蛋白表达与患者年龄、性别、临床分期、近期疗效无关，而bcl-2，p53基因蛋白表达与患者颈部淋巴结转移和病理组织分化程度有关（P＝0.01，P＝0.01）。结论：①放疗可以诱导鼻咽癌组织mdr-1基因产物pgp过表达，使癌细胞获得多药耐药性，并对以后的辅助化疗或同步化疗产生影响，这也可能是引起放疗后化疗耐药的原因之一。②从蛋白质水平了解了鼻咽癌与bcl-2，p53基因的关系，提示这些基因可能参与鼻咽癌细胞的凋亡调节，并对鼻咽癌的发生发展可能起着一定的作用。
Objective：To investigate preliminarily the expression of p-glycoprotein(pgp),a multi-drug resistance gene 1 product，in the patients with nasopharyngeal carcinoma(NPC) pre- and post-radiotherapy.And to observe the expression of bcl-2 gene and p53 gene proteins and their impact on the patients with NPC.Methods: Between March 2001 and August 2002,64 patients with NPC and 10 controls with chronic nasopharyngeal inflammation were enrolled in the study group.All patients had been histologically proven squamous cell carcinomas and none had received neoadjuvant chemotherapy or radiotherapy. pgp,bcl-2 and p53 were detected by immunohistochemistry pre- radiotherapy.Among them, pgp of 48 patiens with NPC was detected by immunohistochemistry post- radiotherapy .Results: The positive rate of pgp ,bcl-2 and p53 proteins expression in untreated NPC was17.19%(11/64)、89.06%(57/64)、76.56%(49/64)，respectively. Bcl-2 and p53 gene proteins expression were significantly higher in the patients with NPC than those in the controls with chronic nasopharyngeal inflammation.The positive rate of pgp expression post-radiotherapy was 75.00%（36/48）,which was significantly higher than that of pgp expression pre-radiotherapy(P<0.001).There was no significantly correlation among the pgp,bcl-2 and p53 proteins expression and age,gender,TNMstaging，but bcl-2 and p53 proteins expression were significantly correlation to cervical lymphonodes metastasis and histologic grade（P=0.01, P=0.01）. pgp expression was significantly induced after radiation compared with expression before treatment(P<0.001).Conclusions: pgp expression was significantly induced by radiation in the patients with NPC. This induction of pgp expression likely confers multidrug resistance to the carcinoma cells and may affect the efficacy of subsequent or concurrent chemotherapy. It may partly explain the lower response to chemotherapy among patients who had previously received radiotherapy. The results of this study support the hypothesis that bcl-2 and p53 genes may be correlations to NPC and they may play an important roles in pathogenesis of NPC.
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