著作: Shimizu Natsumi/Nakajima Nakako Izumi/Tsunematsu Takaaki/Ogawa Ikuko/Kawai Hidehiko/Hirayama Ryoichi/Fujimori Akira/[山田 安希子]/Okayasu Ryuichi/[石丸 直澄]/[高田 隆]/[工藤 保誠]/Selective enhancing effect of early mitotic inhibitor 1 depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells./[The Journal of Biological Chemistry]
(英) Selective enhancing effect of early mitotic inhibitor 1 depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells.
(英) Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side-effects. Early mitotic inhibitor 1 (Emi1) is known to have the function to inhibit anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which ubiquitylates the cell cycle related proteins. It recently has been shown that Emi1 knockdown prevents transition from S to G2 phase by downregulating geminin via APC/C activation. At present anticancer drugs for targeting DNA synthesis to interfere with rapidly dividing cells commonly are used. As Emi1 depletion interferes with completion of DNA synthesis in cancer cells, we thought that Emi1 knockdown might enhance the sensitivity for anticancer agents. Here we confirmed that Emi1 siRNA induced polyploidy for preventing transition from S to G2 phase in several cancer cell lines. Then, we treated Emi1 depleted cells with doxorubicin. Interestingly, increased apoptotic cells were observed after doxorubicin treatment in Emi1 siRNA treated cancer cells. In addition, Emi1 depletion enhanced the sensitivity of X-rays irradiation in cancer cells. Importantly, synergistic effect of Emi1 knockdown in these combination therapies was not observed in normal cells. These results suggest that Emi1 siRNA can be a useful tool for enhancing of sensitivity of cancer cells to anticancer reagents and radiation.
The Journal of Biological Chemistry([The American Society for Biochemistry and Molecular Biology])
|年月日||必須||2013年 5月 3日|