Inhibition of sorcin reverses multidrug resistance of K562/A02 cells and MCF-7/A02 cells via regulating apoptosis-related proteins
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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.
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.
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.
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.
KeywordsSorcin P-gp Multidrug resistance Apoptosis
This work was supported by grants from Natural Science Foundation of China (Grant No. 30873091 and 30971291), Natural Science Foundation of Tianjin (Grant No. 05YFGZGX02800) and National Science and Technology Major Project (Grant No. 2009ZX09103-720).
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