Secreted protein acidic and rich in cysteine antagonizes bufalininduced apoptosis in gastric cancer cells
Bufalin is an active compound in the traditional Chinese medicine Chan Su, which has been shown to induce apoptosis in a range of cancer cell types. However, certain gastric cancer cells are known to be resistant to bufalin. Intracellular secreted protein acidic and rich in cysteine (SPARC) regulates proliferation and apoptosis. This study aimed to evaluate the role of SPARC in bufalininduced apoptosis in SGC7901 and MGC803 gastric cancer cells. SGC7901 cells with high SPARC expression were more resistant to bufalin than MGC803 cells with low SPARC expression. This resistance was significantly reversed by small interfering (si)RNAmediated knockdown of SPARC. Furthermore, it was shown that SPARC negatively regulated bufalininduced intrinsic apoptosis by protecting mitochondrial integrity, decreasing the release of cytoplasmic cytochrome c and increasing the ratio of Bcl2/Bax. In addition, SPARC overcame bufalininduced G2/M phase arrest by increasing levels of Cyclin B1 and Cyclin A protein expression. SPARC also activated cellular survival signals, including Src and Akt, but not extracellular signalregulated kinase. This study demonstrated that SPARC antagonizes bufalininduced apoptosis via inhibition of the intrinsic apoptosis pathway, inhibition of cell cycle arrest and activation of certain pathways involved in proliferation. This provides novel evidence for SPARC as a potential target by which to sensitize gastric cancer cells to bufalin.
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Document Type: Research Article
Affiliations: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Publication date: August 1, 2015
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