Yoshimura Rikio, Matsuyama Masahide, Kawahito Yutaka, Takemoto Yoshiaki, Tsuchida Kenji, Kuratsukuri Katsuyuki, Segawa Yoshihiro, Shinnka Toshiaki, Sano Hajime, Nakatani Tatsuya
Department of Urology, Osaka City University Hospital, Abeno-ku, Osaka 545-8585, Japan.
Int J Mol Med. 2004 Jun;13(6):789-93.
Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenic function. We have demonstrated that the expression of COX-2 was up-regulated in human renal cell carcinoma (RCC), bladder tumor (BT) and prostate cancer (PC). In this study, we examined the effects of COX-2 inhibitors on cell proliferation in RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. COX-2 inhibitors did not induce a reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, showed no inhibition of cell proliferation using COX-2 inhibitors. COX-2 inhibitors could not stop the growth of RCC, BT and PC cells. Typical characteristics of apoptosis, i.e. chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies) and cytoplasmic condensation, did not occur. Although the expression of COX-2 was up-regulated in human RCC, BT and PC tissues, COX-2 inhibitors have only slight anti-proliferative effects against RCC, BT and PC cells through differentiation. Thus, using only down-regulation of arachidonic acid (AA) metabolizing enzyme, COX may be an unsuccessful approach in providing new anti-cancer therapies.
环氧化酶(COX)-2因其血管生成功能在多种癌症的发生发展中起重要作用。我们已证明COX-2在人肾细胞癌(RCC)、膀胱肿瘤(BT)和前列腺癌(PC)中表达上调。在本研究中,我们使用MTT法和Hoechst染色检测了COX-2抑制剂对RCC、BT和PC来源细胞系中细胞增殖的影响。COX-2抑制剂在RCC、BT和PC细胞系的半数最大生长抑制浓度下并未诱导细胞活力降低。此外,在第1、2和3天对细胞进行计数,结果显示使用COX-2抑制剂未抑制细胞增殖。COX-2抑制剂无法阻止RCC、BT和PC细胞的生长。凋亡的典型特征,即染色质浓缩、细胞皱缩、小的膜结合体(凋亡小体)和细胞质浓缩,均未出现。尽管COX-2在人RCC、BT和PC组织中表达上调,但COX-2抑制剂通过分化对RCC、BT和PC细胞仅具有轻微的抗增殖作用。因此,仅通过下调花生四烯酸(AA)代谢酶COX,可能无法成功提供新的抗癌治疗方法。