Mao Jenny T, Fishbein Michael C, Adams Bradley, Roth Michael D, Goodglick Lee, Hong Longsheng, Burdick Marie, Strieter E Robert M, Holmes Carmack, Tashkin Donald P, Dubinett Steven M
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1690, USA.
Clin Cancer Res. 2006 Jan 1;12(1):314-20. doi: 10.1158/1078-0432.CCR-05-1440.
This study evaluated the feasibility of cyclooxygenase-2 (COX-2) inhibition for lung cancer chemoprevention. We hypothesized that treatment with oral Celecoxib, a selective COX-2 inhibitor, would favorably alter the biomarkers of lung cancer risk as measured by the Ki-67 proliferative labeling index (Ki-67 LI).
Twenty active heavy smokers were enrolled into a pilot study and treated with Celecoxib for 6 months. Bronchoscopies with bronchial biopsies were done before and after 6 months of Celecoxib treatment. H&E stain for histologic grading and immunohistochemical examination for Ki-67 LI, COX-2, and survivin were carried out on serially matched biopsy samples to determine responses to treatment.
Treatment with Celecoxib significantly reduced Ki-67 LI in smokers by 35% (P = 0.016), and increased the expression of nuclear survivin by 23% (P = 0.036) without significantly changing that of cytoplasmic survivin.
Our findings suggest that oral Celecoxib may be capable of modulating the proliferation indices and apoptotic balance in bronchial tissue of active smokers.
本研究评估了环氧化酶-2(COX-2)抑制用于肺癌化学预防的可行性。我们假设,口服塞来昔布(一种选择性COX-2抑制剂)治疗会通过Ki-67增殖标记指数(Ki-67 LI)测量,有利地改变肺癌风险的生物标志物。
20名现职重度吸烟者被纳入一项初步研究,并接受塞来昔布治疗6个月。在塞来昔布治疗6个月前后进行支气管镜检查及支气管活检。对连续匹配的活检样本进行苏木精-伊红(H&E)染色以进行组织学分级,并对Ki-67 LI、COX-2和生存素进行免疫组化检查,以确定对治疗的反应。
塞来昔布治疗使吸烟者的Ki-67 LI显著降低35%(P = 0.016),并使核生存素的表达增加23%(P = 0.036),而细胞质生存素的表达没有显著变化。
我们的研究结果表明,口服塞来昔布可能能够调节现职吸烟者支气管组织中的增殖指数和凋亡平衡。