Yunhui Hu1, Xin Cheng, Shuangjing Li, Yuan Zhou, Jianxiang Wang, Tao Cheng, Ming Yang, Dongsheng Xiong. 1. State Key Laboratory of Experimental Hematology, Department of Pharmacy, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.
Abstract
PURPOSE: Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant to chemotherapeutic agents, thus playing an important role in multidrug resistance (MDR). But the mechanisms mediated by sorcin still remain quite elusive. This study aim to explore whether sorcin silencing could restore chemosensitivity in MDR cancer cells and seek to identify the functional mechanisms mediated by sorcin. METHODS: To investigate the mechanisms of sorcin-silencing-induced chemosensitivity, transient expression of sorcin-siRNAs was performed in doxorubicin-induced MDR cell lines, K562/A02 and MCF-7/A02. Sensitivity to five chemotherapeutic agents was evaluated by analysis of cell survival and cell apoptosis. RESULTS: In this report, we show that down-regulation of sorcin did not alter expression or function of P-gp, but actually induced cell apoptosis and chemosensitivity in K562/A02 and MCF-7/A02. We also observe that silencing of sorcin-enhanced chemotherapeutic agent effects partly through regulating apoptosis-related protein, including Bcl-2, Bax, c-jun and c-fos. CONCLUSION: This offers the rationale for the development of therapeutic strategies down-regulating sorcin expression for the treatment of cancer, especially for the reversal of MDR.
PURPOSE:Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant to chemotherapeutic agents, thus playing an important role in multidrug resistance (MDR). But the mechanisms mediated by sorcin still remain quite elusive. This study aim to explore whether sorcin silencing could restore chemosensitivity in MDR cancer cells and seek to identify the functional mechanisms mediated by sorcin. METHODS: To investigate the mechanisms of sorcin-silencing-induced chemosensitivity, transient expression of sorcin-siRNAs was performed in doxorubicin-induced MDR cell lines, K562/A02 and MCF-7/A02. Sensitivity to five chemotherapeutic agents was evaluated by analysis of cell survival and cell apoptosis. RESULTS: In this report, we show that down-regulation of sorcin did not alter expression or function of P-gp, but actually induced cell apoptosis and chemosensitivity in K562/A02 and MCF-7/A02. We also observe that silencing of sorcin-enhanced chemotherapeutic agent effects partly through regulating apoptosis-related protein, including Bcl-2, Bax, c-jun and c-fos. CONCLUSION: This offers the rationale for the development of therapeutic strategies down-regulating sorcin expression for the treatment of cancer, especially for the reversal of MDR.