Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, 261 Huansha Road, Hangzhou, Zhejiang, 310006, China; E-Mails:
Int J Mol Sci. 2010 Oct 19;11(10):3999-4013. doi: 10.3390/ijms11103999.
The report aims to investigate the relationship between the expression of cyclin D1 and Cyclooxgenase-2 (COX-2), thus to explore the molecular mechanisms of the antitumor efficacy of Celecoxib, a COX-2 inhibitor. Human ovarian SKOV-3 carcinoma cell xenograft-bearing mice were treated with Celecoxib by infusing gaster (i.g.) twice/day for 21 days. The mRNA levels of COX-2 and cyclin D1 were determined by RT-PCR. The expression of cyclin D1 at the protein level was detected by immunohistochemistry, while COX-2 protein expression was determined by Western blot. A high-dose of Celecoxib (100 mg/kg) significantly inhibited tumor growth (P < 0.05), and the expression of cyclin D1 was reduced by 61%. Celecoxib decreased the proliferation cell index by 40% (P < 0.001) and increased apoptotic index by 52% (P < 0.05) in high-dose Celecoxib treated group. Our results suggest that the antitumor efficacy of Celecoxib against ovarian cancer in mice may in part be mediated through suppression of cyclin D1, which may contribute to its ability to suppress proliferation.
本报告旨在研究细胞周期蛋白 D1（cyclin D1）和环氧化酶-2（COX-2）的表达之间的关系，从而探讨 COX-2 抑制剂塞来昔布的抗肿瘤作用的分子机制。通过每日两次胃内（i.g.）输注塞来昔布，对荷有人卵巢 SKOV-3 癌异种移植瘤的小鼠进行 21 天的治疗。通过 RT-PCR 测定 COX-2 和 cyclin D1 的 mRNA 水平。通过免疫组织化学检测 cyclin D1 的蛋白水平，通过 Western blot 检测 COX-2 蛋白的表达。高剂量塞来昔布（100mg/kg）显著抑制肿瘤生长（P < 0.05），cyclin D1 的表达降低了 61%。塞来昔布使增殖细胞指数降低了 40%（P < 0.001），并使高剂量塞来昔布治疗组的凋亡指数增加了 52%（P < 0.05）。我们的结果表明，塞来昔布对小鼠卵巢癌的抗肿瘤作用可能部分是通过抑制 cyclin D1 介导的，这可能有助于其抑制增殖的能力。
