Oncotarget

Research Papers:

Mcl-1 stabilization confers resistance to taxol in human gastric cancer

Wu Shuang, Lili Hou, Yan Zhu, Qun Li and Wanglai Hu _

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Oncotarget. 2017; 8:82981-82990. https://doi.org/10.18632/oncotarget.20222

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Abstract

Wu Shuang1,*, Lili Hou2,*, Yan Zhu3,*, Qun Li1 and Wanglai Hu1

1Department of Immunology, Anhui Medical University, Hefei, China

2Department of Clinical Nutriology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

3Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

*These authors have contributed equally to this work

Correspondence to:

Wanglai Hu, email: [email protected]

Keywords: Mcl-1, PI3K/Akt, Taxol-resistance

Received: March 08, 2017    Accepted: July 26, 2017    Published: August 12, 2017

ABSTRACT

Taxol has been extensively used as an antineoplastic drug to treat human gastric cancer. However, the acquired drug resistance invariably develops and greatly limits the therapeutic efficacy of Taxol. Identification of the underlying resistance mechanisms may inform the development of new therapies of gastric cancers to Taxol treatment. Here we report that upregulation of Mcl-1 (Myeloid cell leukemia-1) confers acquired resistance to Taxol in human gastric cancer. Mcl-1 is shown to be stabilized in Taxol -resistant gastric cancer cells because of the hyper-activation of the PI3K/Akt signaling pathway. The increased Mcl-1 prevents of the permeabilization of the outer mitochondrial membrane, thereby blocking the Taxol-induced apoptosis. Furthermore, inhibition of Mcl-1 or PI3K/Akt pathway significantly reversed the resistant phenotype of Taxol-resistant human gastric cancer cells. Taken together, our findings broaden the view of PI3K/Akt pathway as an important regulator in Taxol acquired resistance, and implicate Mcl-1 as a specific therapeutic target for the treatment of Taxol-resistant human gastric cancer.


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