三氧化二砷对鼻咽癌放疗增敏作用及其机制的研究

Radiosensitization of arsenic trioxide in nasopharyngeal carcinoma and its mechanism

目的:探讨三氧化二砷(As2O3)注射液对鼻咽癌放疗增敏作用与肿瘤血管生成素表达的关系。方法:将74例鼻咽癌患者随机分为单纯放疗组(放疗组)和As2O3放射增敏组(增敏组),观察两组患者鼻咽肿瘤消退情况。每个病例在治疗前及放疗20Gy后24h各取材1次。免疫组化SP法检测血管生成素1(Ang-1)和血管生成素2(Ang-2)蛋白表达。结果:放疗40Gy时增敏组和放疗组的鼻咽肿瘤消退率分别为43.6%(17/39)和20.0%(7/35),χ2=4.684,P=0.003。增敏组Ang-1和Ang-2蛋白在放射治疗剂量20Gy时均表达下调,z分别为-2.147和-2.985,P值分别为0.032和0.003。在40Gy肿瘤消退组,Ang-2蛋白下调,z=-2.183,P=0.029。结论:As2O3注射液对鼻咽癌患者放射治疗具有增敏作用,其增敏机制可能与Ang-1和Ang-2蛋白抑制肿瘤血管形成有关。

OBJECTIVE： To explore the relationship between the expression of angiopoietins （Ang-1 and Ang-2） and arsenic trioxide （As2O3 ） radiosensitization in nasopharyngeal carcinoma（NPC）. METHODS： Seventy-four patients with NPC were randomized into conventional fractionation radiotherapy （CFR） group and CFR＋ As2O3 group. The regressions of nasopharyngeal lesions was compared between two groups. Every patient had biospy twice on the pre-treatment and after 24 h of post-radiation of 20 Gy. Ang-1 and Ang-2 protein expression was determined by immunhistochemical method. RESULTS： When irradiation dose was 40 Gy, the completely regression rates of nasopharyngeallesion were 20. 0%（7/35） in CFR group and 43. 6% （17/39） in CFR＋ As2O3 group, respectively, Х^2 =4. 684,P=0. 003. There were significant reduction of Ang-1 and Ang-2 protein expression between pre-and post-treatment in CFR ＋ As2O3 group（z=- 2. 147, P= 0. 032; z=-2. 985, P=0. 003）. In nasopharyngeal lesion complete regression group, the difference of expression Ang-2 protein down-regulation was statistically significant between pre-and post-treatment, z = - 2. 183, P = 0. 029. CONCLUSIONS ： These results indicate that As2O3 can synergistically enhance radiosensitivity of patients with NPC. The mechanism of radiosensitivity activity may be due, at least in part, to inhibited tumor angiogenesis by down-regulation the expression of Ang-1 and Ang-2 protein.