三氧化二砷对鼻咽癌患者放疗增敏作用与增殖和凋亡相关蛋白关系

目的 探讨三氧化二砷（arsenic trioxide,ATO）放疗增敏对鼻咽癌增殖和凋亡相关蛋白的影响.方法 将74例T1～4N0～1M0期鼻咽癌患者随机分为单纯放疗（简称放疗组）和ATO增敏组（简称增敏组）,观察两组患者放射治疗40Gy时鼻咽肿瘤和颈部淋巴结消退情况.每个患者在治疗前及放疗20 Gy后的24 h各取材1次.免疫组化EnVision法测定增殖核抗原（PCNA）、Bcl-2、Bax和p53蛋白表达.结果 放射治疗40 Gy时增敏组和放疗组的鼻咽肿瘤消退率分别43.6%（17/39例）和20.0%（7/35例）,差异有显著性（χ^2=4.684,P=0.003）;两组颈部淋巴结消退速度差异无显著性.治疗剂量为20 Gy的PCNA、Bcl-2、Bax和p53蛋白表达均下调,但仅增敏组PCNA和Bax差异有显著性（Z值分别-2.449和-3.031,P值分别为0.014和0.002）.两组24例肿瘤消失患者中,PCNA、Bax和p53蛋白下调与治疗前比较,差异有显著性（Z值分别为-2.656、-2.359和-1.999;P值分别为0.008、0.018和0.046）;肿瘤未消失患者中,仅PCNA下调,与治疗前比较差异有显著性（Z=-32.815,P=0.015）.结论 ATO对鼻咽癌患者有放射增敏作用,其增敏机制可能通过下调PCNA及凋亡相关蛋白,抑制肿瘤增殖和诱导凋亡有关.

Relationship between Radiotherapy Enhancing Effect of Arsenic Trioxide and the Proliferation and Apoptosis of Related Protein in Nasopharyngeal Carcinoma Patients

OBJECTIVE: To explore the mechanism of arsenic trioxide (ATO) in enhancing radiotherapy in nasopharyngeal carcinoma (NPC) patients. METHODS: Seventy-four patients with NPC of T(1-4) N(0-1)M0 were randomized into two groups: 35 patients in Group A were treated with conventional radiotherapy alone, and the 39 in Group B received radiotherapy and additional administering of ATO. The regressions of nasopharyngeal lesions and cervical lymph nodes were compared between the two groups at 40 Gy of radiation was given. And biopsy of the tissue from NPC was taken before treatment and 24 h after radiation of 20 Gy to determine the-expressions of proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and p53 protein by immunohistochemistry. RESULTS: When irradiation for 40 Gy, the completely regression rates of nasopharyngeal lesion were 20.0% (7/35) in Group A and 43.6% (17/39) in Group B, showing significant difference between them (chi2 = 4.684, P = 0.003), but no significant difference was shown between the two groups in regression rate of cervical lymph node. Expression of PCNA, Bax, Bcl-2 and p53 protein was reduced in both groups, but significant difference only showed between pre- and post-treatment in PCNA (Z = -2.449, P = 0.014) and Bax protein (Z = -3.031, P = 0.002) in Group B. Significantly reduction of PCNA (Z = -2.656, P = 0.008), Bax (Z = -2.359, P = 0.018) and p53 protein (Z = -1.999, P = 0.046) in patients with complete tumor regression at radiation for 20 Gy, while in those with no complete tumor regression only PCNA showed significant reduction (Z = -32.815, P = 0.015). CONCLUSION: ATO shows effect in enhancing radiotherapy on NPC patients, its mechanism might be associated with the down-regulation of PCNA and apoptosis related protein and the inhibition on tumor proliferation and apoptosis inducing.