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Early apoptosis and cell death induced by ATX-S10Na ( Ⅱ )-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells
作者姓名:Mitsunaga M  Tsubota A  Nariai K  Namiki Y  Sumi M  Yoshikawa T  Fujise K
作者单位:Makoto Mitsunaga(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan;Division of Gastroenterology and Hepatology, Department of Internal Medicine,Jikei University School of Medicine, Tokyo, Japan) ; Akihito Tsubota(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan) ; Kohichi Nariai(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan) ; Yoshihisa Namiki(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan) ; Makoto Sumi(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan) ; Tetsuya Yoshikawa(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan) ; Kiyotaka Fujise(Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan;Division of Gastroenterology and Hepatology, Department of Internal Medicine,Jikei University School of Medicine, Tokyo, Japan) ;
基金项目:Supported by a grant from the Jikei University School of Medicine
摘    要:AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ). METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin Ⅴ assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-xL, were decreased in Bax- and p53-independent manner. CONCLUSION: Our results indicate that eady apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na (Ⅱ) are mediated by p53- Bax network and low levels of Bcl-2 and Bcl-xL proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

关 键 词:结肠癌  癌细胞  细胞凋亡  细胞死亡  光动力疗法  ATX-S10Na  介导  BAX  P53
收稿时间:2006 Oct 20

Early apoptosis and cell death induced by ATX-S10Na (II)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells
Mitsunaga M,Tsubota A,Nariai K,Namiki Y,Sumi M,Yoshikawa T,Fujise K.Early apoptosis and cell death induced by ATX-S10Na (II)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells[J].World Journal of Gastroenterology,2007,13(5):692-698.
Authors:Mitsunaga Makoto  Tsubota Akihito  Nariai Kohichi  Namiki Yoshihisa  Sumi Makoto  Yoshikawa Tetsuya  Fujise Kiyotaka
Institution:Institute of Clinical Medicine and Research, Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan.
Abstract:AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (II). METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-x(L), were decreased in Bax- and p53-independent manner. CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na (II) are mediated by p53-Bax network and low levels of Bcl-2 and Bcl-x(L) proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.
Keywords:Photodynamic therapy  ATX-S10Na (Ⅱ)  Apoptosis  Bax  p53
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