Cyclooxygenase-2 promotes prostate cancer progression
Cyclooxygenase-2 promotes prostate cancer progression
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DOI：
10.1002/pros.10152
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发表时间：
2002-11-01
期刊：
影响因子：
2.8
通讯作者：
Mizokami, A
中科院分区：
文献类型：
--
作者：
Fujita, H;Koshida, K;Mizokami, A
背景资料。环氧合酶(COX)-2是COX的一种诱导型亚型，在前列腺癌中有表达。已有研究报道COX-2过表达与多种肿瘤的发生、生长、血管生成、细胞凋亡及侵袭性有关。方法：为直接探讨COX-2在前列腺癌中的作用，我们将人COX-2全长cDNA稳定地导入内源性COX-2低水平表达的LNCaP细胞(LNCaP-COX-2)。结果与亲本细胞和对照细胞相比，COX-2基因在LNCaP-2LNCaP-COX-2细胞中的表达水平和COX活性显著升高。COX-2过表达促进了肿瘤的体外增殖和体内生长。然而，促肿瘤作用与雄激素受体(AR)表达水平和AR活性的变化无关。此外，COX-2介导的花生四烯酸代谢的主要代谢产物的加入不会改变LNCaP-COX-2细胞的体外增殖。LNCaP-COX-2细胞分泌的血管内皮生长因子(VEGF)蛋白增加，提示COX-2诱导的血管生成促进了肿瘤的活体生长。结论COX-2参与了前列腺癌的进展，提示COX-2可能部分通过增加血管内皮生长因子来介导这一作用。
BACKGROUND. Cyclooxygenase (COX)-2, an inducible isoform of COX, has been observed to be expressed in prostate cancer. Several studies have reported that COX-2 overexpression is associated with carcinogenesis, cell growth, angiogenesis, apoptosis, and invasiveness in a variety of tumor types.METHODS. To investigate the function of COX-2 in prostate cancer directly, we stably transfected human full-length COX-2 cDNA into LNCaP cells (LNCaP-COX-2), which express low levels of endogenous COX-2.RESULTS. The level of COX-2 mRNA and protein and the COX activity in COX-2 LNCaP-COX-2 cells was significantly increased compared with parent and control-transfected cells. Overexpression of COX-2 increased both proliferation in vitro and tumor growth rate in vivo. However, the pro-tumor effect was neither associated with changes of androgen receptor (AR) expression level nor AR activity. Furthermore, addition of the major metabolites of COX-2-mediated arachidonic acid metabolism did not alter the proliferation of LNCaP-COX-2 cells in vitro. LNCaP-COX-2 cells had increased secretion of vascular endothelial growth factor (VEGF) protein, suggesting that angiogenesis induced by COX-2 stimulates tumor growth in vivo.CONCLUSION. These data demonstrate that COX-2 contributes to prostate cancer progression and suggest that it mediates this effect, in part, through increased VEGF.