critical role of heat shock protein 27 in bufalin-induced apoptosis in human osteosarcomas a proteomic-based research关键作用的热休克蛋白27在人类骨肉瘤proteomic-based bufalin-induced细胞凋亡的研究.pdfVIP

Critical Role of Heat Shock Protein 27 in Bufalin-Induced Apoptosis in Human Osteosarcomas: A Proteomic-Based Research 1. 1. 3. 1 1 1 1 Xian-biao Xie , Jun-qiang Yin , Li-li Wen , Zhen-hua Gao , Chang-ye Zou , Jin Wang , Gang Huang , 1 4 1 2 1 Qing-lian Tang , Chiara Colombo , Wei-ling He , Qiang Jia *, Jing-nan Shen * 1 Bone and Soft Tissue Tumor Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, 2 The Institute of Biology, Guizhou Academy of Sciences, Guiyang, China, 3 Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, China, 4 Department of Surgery, Istituto Nazionale Tumori, Milan, Italy Abstract Bufalin is the primary component of the traditional Chinese herb ‘‘Chan Su’’. Evidence suggests that this compound possesses potent anti-tumor activities, although the exact molecular mechanism(s) is unknown. Our previous study showed that bufalin inhibited growth of human osteosarcoma cell lines U2OS and U2OS/MTX300 in culture. Therefore, this study aims to further clarify the in vitro and in vivo anti-osteosarcoma effects of bufalin and its molecular mechanism of action. We found bufalin inhibited both methotrexate (MTX) sensitive and resistant human osteosarcoma cell growth and induced G2/ M arrest and apoptosis. Using a comparative proteomics approach, 24 differentially expressed proteins following bufalin treatment were identified. In particular, the level of an anti-apoptotic protein, heat shock protein 27 (Hsp27), decreased remarkably. The down-regulation of Hsp27 and alterations of its partner signaling molecules (the decrease in p-Akt