Antitumor effect of the selective COX-2 inhibitor celecoxib on endometrial adenocarcinoma in vitro and in vivo
- Authors:
- Yitao Xiao
- Yincheng Teng
- Rui Zhang
- Laimin Luo
View Affiliations
Affiliations: Department of Gynecology and Obstetrics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
- Published online on: September 24, 2012 https://doi.org/10.3892/ol.2012.936
-
Pages:
1219-1224
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Abstract
The aim of this study was to investigate the antitumor effect of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on endometrial adenocarcinoma in mice. Various amounts of celecoxib were added to HEC-1B cells in vitro for different durations. Cell cycle and apoptosis were analyzed using flow cytometry. HEC-1B cytostasis, invasiveness and COX-2 expression were examined by MTT, transwell cabin and western blot assays, respectively. An in vivo human endometrial adenocarcinoma model was established in BALB/c nude mice using HEC-1B cells. For two weeks, the celecoxib groups were treated with celecoxib 2 or 4 mg/day via oral administration and the control group was treated with saline. Tumor volume, growth curves and the inhibition rate (IR) were recorded. COX-2 expression levels and microvessel density (MVD) were investigated using an immunohistochemical technique. In the celecoxib groups, cell proliferation was significantly inhibited in a concentration- and time-dependent manner. The proportion of cells in the G0/G1 phase increased within 24 h after the addition of celecoxib whereas those in the S and G2/M phases decreased with an increasing apoptosis peak (sub-G1) and apoptosis rate. The microporous Matrigel‑coated polycarbonate membrane of the Transwell cabin was traversable for the HEC-1B cells. The invasiveness was attenuated when the celecoxib concentration was increased. The tumor growth was also greatly inhibited when the celecoxib concentration was increased. The tumor IRs were 32.4 and 48.6% following treatment with 2 and 4 mg/day celecoxib, respectively. COX-2 was mainly expressed in the cytoplasm of the tumor cells. In the celecoxib groups, the COX-2 expression levels were concentration-dependent. The COX-2 expression level and MVD decreased when the celecoxib concentration was increased. The results of dependability analysis revealed that the COX-2 expression level was positively correlated with MVD (r=0.921; P<0.01). The antitumor effect of celecoxib on endometrial adenocarcinoma in nude mice may be related to the inhibition of COX-2 expression and microangiogenesis.
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