sensitization of glioma cells to tamoxifen-induced apoptosis by pl3-kinase inhibitor through the gsk-3ββ-catenin signaling pathway敏感的神经胶质瘤细胞tamoxifen-induced通过gsk-3ββ-catenin pl3-kinase抑制剂细胞凋亡信号通路.pdfVIP

Sensitization of Glioma Cells to Tamoxifen-Induced Apoptosis by Pl3-Kinase Inhibitor through the GSK-3b/b- Catenin Signaling Pathway 1 1 1 2 1 1 1 1 Cuixian Li , Chun Zhou , Shaogui Wang , Ying Feng , Wei Lin , Sisi Lin , Ying Wang , Heqing Huang , 1 3 1 Peiqing Liu , Yong-Gao Mu *, Xiaoyan Shen * 1 Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China, 2 Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China, 3 Department of Neurosurgery/Neuro-oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China Abstract Malignant gliomas represent one of the most aggressive types of cancers and their recurrence is closely linked to acquired therapeutic resistance. A combination of chemotherapy is considered a promising therapeutic model in overcoming therapeutic resistance and enhancing treatment efficacy. Herein, we show by colony formation, Hochest 33342 and TUNEL staining, as well as by flow cytometric analysis, that LY294002, a specific phosphatidylinositide-3-kinase (PI3K) inhibitor, enhanced significantly the sensitization of a traditional cytotoxic chemotherapeutic agent, tamoxifen-induced apoptosis in C6 glioma cells. Activation of PI3K signaling pathway by IGF-1 protected U251 cells from apoptosis induced by combination treatment of LY294002 and tamoxifen. Interference of PI3K signaling pathway by PI3K subunit P85 siRNA enhanced the sensitization of U251 glioma cells to tamoxifen -induced apoptosis. By Western blotting, we found that combination treatment showed lower lev