Wu William Ka Kei, Sung Joseph Jao Yiu, Wu Ya Chun, Li Hai To, Yu Le, Li Zhi Jie, Cho Chi Hin
Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Biochem Biophys Res Commun. 2009 Apr 24;382(1):79-84. doi: 10.1016/j.bbrc.2009.02.140. Epub 2009 Mar 1.
Evolving evidence supports that cyclooxygenase-1 (COX-1) takes part in colon carcinogenesis. The effects of COX-1 inhibition on colon cancer cells, however, remains obscured. In this study, we demonstrate that COX-1 inhibitor sc-560 inhibited colon cancer cell proliferation with concomitant G(0)/G(1)-phase cell cycle arrest. The anti-proliferative effect was associated with down-regulation of c-Fos, cyclin E(2) and E(2)F-1 and up-regulation of p21(Waf1/Cip1) and p27(Kip1). In addition, sc-560 induced macroautophagy, an emerging mechanism of tumor suppression, as evidenced by the formation of LC3(+) autophagic vacuoles, enhanced LC3 processing, and the accumulation of acidic vesicular organelles and autolysosomes. In this connection, 3-methyladenine, a Class III phosphoinositide 3-kinase inhibitor, significantly abolished the formation of LC3(+) autophagic vacuoles and the processing of LC3 induced by sc-560. To conclude, this study reveals the unreported relationship between COX-1 and proliferation/macroautophagy of colon cancer cells.
越来越多的证据支持环氧化酶-1（COX-1）参与结肠癌的发生。然而，COX-1抑制对结肠癌细胞的影响仍不清楚。在本研究中，我们证明COX-1抑制剂sc-560抑制结肠癌细胞增殖，并伴随G(0)/G(1)期细胞周期停滞。抗增殖作用与c-Fos、细胞周期蛋白E(2)和E(2)F-1的下调以及p21(Waf1/Cip1)和p27(Kip1)的上调有关。此外，sc-560诱导了大自噬，这是一种新出现的肿瘤抑制机制，表现为LC3(+)自噬泡的形成、LC3加工增强以及酸性囊泡细胞器和自溶酶体的积累。在此方面，III类磷酸肌醇3激酶抑制剂3-甲基腺嘌呤显著消除了sc-560诱导的LC3(+)自噬泡的形成和LC3的加工。总之，本研究揭示了COX-1与结肠癌细胞增殖/大自噬之间未报道的关系。
