Li Wei, Cai Jia-Hui, Zhang Jun, Tang Yun-Xian, Wan Liang
Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang, China.
Int J Mol Sci. 2012;13(8):9741-9753. doi: 10.3390/ijms13089741. Epub 2012 Aug 3.
The present study was designed to investigate the effects of cyclooxygenase (COX) inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor) alone, 3 mg/kg SC-560 (a COX-1 selective inhibitor) alone by gavage twice a day, 20 mg/kg taxol alone by intraperitoneally (i.p.) once a week, or celecoxib/taxol, SC-560/celecoxib, SC-560/taxol or SC-560/celecoxib/taxol, for three weeks. To test the mechanism of the combination treatment, the index of cell proliferation and expression of cyclin D1 in tumor tissues were determined by immunohistochemistry. The mean tumor volume in the treated groups was significantly lower than control (p < 0.05), and in the three-drug combination group, tumor volume was reduced by 58.27% (p < 0.01); downregulated cell proliferation and cyclin D1 expression were statistically significant compared with those of the control group (both p < 0.01). This study suggests that the effects of COX selective inhibitors on the growth of tumors and decreased cell proliferation in a SKOV-3 cells mouse xenograft model were similar to taxol. The three-drug combination showing a better decreasing tendency in growth-inhibitory effect during the experiment may have been caused by suppressing cyclin D1 expression.
本研究旨在探讨环氧化酶(COX)抑制剂与紫杉醇联合应用对人卵巢SKOV - 3癌细胞异种移植小鼠中细胞周期蛋白D1和Ki - 67表达的影响。动物分别接受以下处理:每天两次灌胃给予100 mg/kg塞来昔布(一种COX - 2选择性抑制剂)、每天两次灌胃给予3 mg/kg SC - 560(一种COX - 1选择性抑制剂)、每周一次腹腔注射20 mg/kg紫杉醇,或给予塞来昔布/紫杉醇、SC - 560/塞来昔布、SC - 560/紫杉醇或SC - 560/塞来昔布/紫杉醇,持续三周。为了检测联合治疗的机制,通过免疫组织化学测定肿瘤组织中的细胞增殖指数和细胞周期蛋白D1的表达。治疗组的平均肿瘤体积显著低于对照组(p < 0.05),在三联药物组合组中,肿瘤体积减少了58.27%(p < 0.01);与对照组相比,细胞增殖下调和细胞周期蛋白D1表达下调具有统计学意义(均为p < 0.01)。本研究表明,在SKOV - 3细胞小鼠异种移植模型中,COX选择性抑制剂对肿瘤生长和细胞增殖减少的作用与紫杉醇相似。在实验过程中,三联药物组合在生长抑制作用方面表现出更好的下降趋势,这可能是由于抑制了细胞周期蛋白D1的表达所致。