Yun Chen1,2, Cheng-Hung Lee3,4, Bor-Yuan Tseng1, Ya-Hui Tsai1,2,5, Huang-Wen Tsai1, Chao-Ling Yao6,3, Sheng-Hong Tseng7. 1. Department of Surgery, Far Eastern Memorial Hospital, New Taipei, Taiwan, R.O.C. 2. Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan, Taiwan, R.O.C. 3. Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan, Taiwan, R.O.C. 4. Department of General Surgery, Buddhist Dalin Tzu Chi Hospital, Chia-Yi and School of Medicine, Tzu Chi University, Hualien, Taiwan, R.O.C. 5. Department of Materials and Textiles, Oriental Institute of Technology, New Taipei, Taiwan, R.O.C. 6. Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan, Taiwan, R.O.C. d897601@alumni.nthu.edu.tw yao@saturn.yzu.edu.tw shenghongtseng@gmail.com. 7. Department of Surgery, National Taiwan University Hospital, and National Taiwan University College of Medicine, Taipei, Taiwan, R.O.C. d897601@alumni.nthu.edu.tw yao@saturn.yzu.edu.tw shenghongtseng@gmail.com.
Abstract
BACKGROUND/AIM: AZD8055 is an inhibitor of mammalian target of rapamycin (mTOR) that can suppress both mTOR complex 1 (mTORC1) and mTORC2. This study investigated the antitumor effects of AZD8055 on colon cancer. MATERIALS AND METHODS: The effects of AZD8055 on proliferation, apoptosis, and cell cycle of colon cancer cells, and tumor growth in a mouse colon cancer model were studied. RESULTS: AZD8055 significantly inhibited proliferation and induced apoptosis of colon cancer cells (p<0.05). The phosphorylation of both AKT and S6 kinase 1 (S6K1) was suppressed by AZD8055. AZD8055 also induced G0/G1 cell-cycle arrest, reduced cyclin D1 and increased p27 expression, and suppressed the levels of phospho-cyclin-dependent kinase 2 and phospho-retinoblastoma. Compared to the control, oral administration of AZD8055 significantly suppressed tumor growth in mice (p<0.05). CONCLUSION: AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression. Copyright
BACKGROUND/AIM: AZD8055 is an inhibitor of mammalian target of rapamycin (mTOR) that can suppress both mTOR complex 1 (mTORC1) and mTORC2. This study investigated the antitumor effects of AZD8055 on colon cancer. MATERIALS AND METHODS: The effects of AZD8055 on proliferation, apoptosis, and cell cycle of colon cancer cells, and tumor growth in a mousecolon cancer model were studied. RESULTS:AZD8055 significantly inhibited proliferation and induced apoptosis of colon cancer cells (p<0.05). The phosphorylation of both AKT and S6 kinase 1 (S6K1) was suppressed by AZD8055. AZD8055 also induced G0/G1 cell-cycle arrest, reduced cyclin D1 and increased p27 expression, and suppressed the levels of phospho-cyclin-dependent kinase 2 and phospho-retinoblastoma. Compared to the control, oral administration of AZD8055 significantly suppressed tumor growth in mice (p<0.05). CONCLUSION:AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression. Copyright
Authors: Jose M Ayuso; Ross Vitek; Adam D Swick; Melissa C Skala; Kari B Wisinski; Randall J Kimple; Paul F Lambert; David J Beebe Journal: Sci Rep Date: 2019-08-28 Impact factor: 4.379
Authors: Tianna Zhao; I-Mei Siu; Tara Williamson; Haoyu Zhang; Chenchen Ji; Peter C Burger; Nick Connis; Jacob Ruzevick; Menghang Xia; Lucia Cottone; Adrienne M Flanagan; Christine L Hann; Gary L Gallia Journal: J Pathol Date: 2021-07-28 Impact factor: 9.883