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PUMA mediates the anti-cancer effect of osimertinib in colon cancer cells

Authors Guo L, Huang S, Wang X

Received 11 April 2017

Accepted for publication 15 August 2017

Published 3 November 2017 Volume 2017:10 Pages 5281—5288

DOI https://doi.org/10.2147/OTT.S139382

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati

Lingchuan Guo,1,* Shan Huang,1,* Xinwei Wang2

1Department of Pathology, Hospital of Suzhou University, Suzhou, 2Department of Oncology, Tumor Hospital of Jiangsu Province, Nanjing, Jiangsu, China

*These authors contributed equally to this work

Abstract: Osimertinib, an irreversible EGFR/HER2 inhibitor, has been found to be effective in the cancer cell with EGFR gene mutations in preclinical lung cancer models. However, the effect of osimertinib in colorectal cancer (CRC) cells is unclear. In the present study, we investigated how osimertinib suppresses CRC cells growth and potentiates effects of other chemotherapeutic drugs. We found that p73-mediated osimertinib-induced p53 upregulated modulator of apoptosis (PUMA) expression irrespective of p53 status following PI3K/AKT pathway inhibition in CRC cells. Furthermore, PUMA is required for osimertinib-induced apoptosis. In addition, osimertinib also synergized with 5-FU to induce significant apoptosis via PUMA in CRC cells. These results demonstrated a critical role of PUMA in mediating the anticancer effects of osimertinib and suggest that PUMA induction can be used as an indicator of osimertinib sensitivity.

Keywords: PUMA, osimertinib, apoptosis, p73, CRC

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