Bortezomib enhances radiation-induced apoptosis in solid tumors by inhibiting CIP2A

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• 作者：Chao-Yuan Huang^c ; ^d ; Chia-Cheng Wei^a ; ^b ; Kuei-Chiu Chen^a ; ^b ; Hui-Ju Chen^a ; ^b ; Ann-Lii Cheng^b ; ^c ; Kuen-Feng Chen^a ; ^b ; ^{kfchen1970@ntu.edu.tw}
• 关键词：HCC ; hepatocellular carcinoma ; PP2A ; protein phosphatase 2A ; CIP2A ; cancerous inhibitor of PP2A ; PI3K ; phosphatidylinositol-3-kinase ; PDK1 ; phosphatidylinositol-3-kinase dependent 1 ; PARP ; poly (ADP-ribose) polymerase ; DMEM ; Dulbecco&rsquo ; s modified Eagl
• 刊名：Cancer Letters
• 出版年：2012
• 出版时间：1 April 2012
• 年：2012
• 卷：317
• 期：1
• 页码：9-15
• 全文大小：816 K

文摘

Previously, we demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) mediates bortezomib-induced apoptosis in hepatocellular carcinoma cells. Herein, we report that bortezomib sensitizes solid tumor cells to radiation-induced apoptosis. Treatment with a combination of bortezomib and radiation downregulated CIP2A in a dose-dependent manner in solid tumor cells. Knockdown of CIP2A enhanced radiation-induced apoptosis in cancer cells, and ectopic expression of CIP2A in cancer cells abolished radiation-induced apoptosis. Finally, our in vivo data showed that bortezomib and radiation combination treatment decreased tumor growth significantly. Thus, bortezomib sensitized solid tumor cells to radiation through the inhibition of CIP2A.