Idelalisib induces PUMA-dependent apoptosis in colon cancer cells

Shida Yang; Zhiyong Zhu; Xiaobing Zhang; Ning Zhang; Zhicheng Yao

doi:10.18632/oncotarget.14043

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Research Papers:

Idelalisib induces PUMA-dependent apoptosis in colon cancer cells

Shida Yang, Zhiyong Zhu, Xiaobing Zhang, Ning Zhang and Zhicheng Yao _

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Oncotarget. 2017; 8:6102-6113. https://doi.org/10.18632/oncotarget.14043

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Abstract

Shida Yang1, Zhiyong Zhu3, Xiaobing Zhang1, Ning Zhang4, Zhicheng Yao2

1Department of Laboratory Medicine, The People’s Hospital of Liaoning Province, Shenyang, China

2Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, China

3Department of Orthopedics, The People’s Hospital of Liaoning Province, Shenyang, China

4Department of Laboratory Medicine, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China

Correspondence to:

Zhicheng Yao, email: [email protected]

Keywords: idelalisib, colon cancer, PUMA, apoptosis, GSK3β

Received: July 29, 2016 Accepted: December 12, 2016 Published: December 20, 2016

ABSTRACT

Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. PUMA is necessary for idelalisib-induced apoptosis in colon cancer cells. Idelalisib also synergized with 5-FU or regorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and antitumor effect of idelalisib in xenograft model. These results demonstrate a critical role of PUMA in mediating the anticancer effects of idelalisib in colon cancer cells and suggest that PUMA induction can be used as an indicator of idelalisib sensitivity, and also have important implications for it clinical applications.

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PII: 14043

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Research Papers:

Idelalisib induces PUMA-dependent apoptosis in colon cancer cells

Abstract