重组人p53腺病毒注射液逆转鼻咽癌化疗耐药的研究

目的:探讨重组人p53腺病毒(rAd-p53)瘤内注射前后的鼻咽癌原发灶中P糖蛋白(P-glycoprotein,P-gp)、多药耐药相关蛋白(multi-drug resistance-associated protien,MRP)和肺耐药蛋白(lungresistance-related protein,LRP)的表达情况及其意义。方法:71例确诊中晚期鼻咽癌的患者随机分为3组:基因治疗组(27例,行-rAd-p53瘤内注射+同步放化疗)、常规放化疗组(24例)和单纯放疗组(20例)。12例同期门诊活检病理为鼻咽黏膜慢性炎患者作为对照。分别收集治疗前、治疗中鼻咽部瘤体组织标本。采用免疫组化法检测鼻咽癌组织中P-gp、MRP和LRP的表达情况。结果:鼻咽癌组中P-gp、MRP及LRP阳性表达率分别为57.7%(41/71)、57.7%(41/71)、53.5%(38/71),黏膜慢性炎组未见P-gp、MRP及LRP表达。基因治疗组治疗前、后原发灶P-gp、MRP和LRP蛋白阳性表达率分别为55.6%和25.9%、63.0%和33.3%、59.3%和25.9%,差异有统计学意义。常规放化疗组治疗前、后鼻咽癌原发灶P-gp、MRP和LRP蛋白阳性表达率分别为62.5%和79.2%、58.3%和70.8%、50%和58.3%,差异无统计学意义。单纯放疗组治疗前、后鼻咽癌原发灶P-gp、MRP和LRP蛋白阳性表达率分别为55.0%和55.0%、50%和40%、50%和55%,差异无统计学意义。结论:P-gp、MRP和LRP与鼻咽癌的内源性耐药相关;p53基因治疗可一定程度逆转鼻咽癌耐药,可能是其治疗鼻咽癌的作用机制之一。

Reversal of chemo-resistance in advanced nasopharyngeal carcinoma by injection of recombinant human p53 adenovirus

Objective To investigate the expressions of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP), and lung resistance-related protein (LRP) in advanced nasopharyngeal carcinoma (NPC) before and after the intratumoral injection with recombinant human p53 adenovirus (rAd-p53). Methods Seventy-one patients who were diagnosed as advanced NPC were randomly divided into 3 groups: the gene therapy group (n = 27) received intratumoral injection of rAd-p53 and concurrent chemo-radiotherapy, the conventional group (n = 24), and the radiotherapy group (n = 20). 12 patients with chronic nasopharyngitis were enrolled as control group. Clinical data and the nasopharyngeal tumor tissues were collected. The two-step immunohistochemical was used to detect the expressions of P-gp, MRP, and LRP in the primary tumor tissue of NPC. Results The expression rates of P-gp, MRP, and LRP in patients with NPC were 57.7% (41/71), 57.7% (41/71), and 55.6% (38/71), respectively. P-gp, MRP, and LRP were not expressed in control group. In gene therapy group, the expression rates of P-gp, MRP, and LRP were 55.6%, 63.0%, and 59.3% before treatment, were 25.9%, 33.3%, and 25.9% after treatment (P < 0.05). Those in conventional group were 62.5%, 58.3%, and 50% before treatment, were 79.2%, 70.8%, and 58.3% after treatment (P < 0.05). And those in radiotherapy group were 55%, 50%, and 50% before treatment, were 55%, 40%, and 55% after treatment (P < 0.05). Conclusion P-gp, MRP, and LRP are associated with the intrinsic drug resistance in NPC. The rAd-p53 intratumoral injection can reverse chemo-resistance of NPC.