Supplementary Figure S1-2 from Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer

Dou, Qianhui; Chen, Hai-Ning; Wang, Kui; Yuan, Kefei; Lei, Yunlong; Li, Kai; Lan, Jiang; Chen, Yan; Huang, Zhao; Xie, Na; Zhang, Lu; Xiang, Rong; Nice, Edouard C.; Wei, Yuquan; Huang, Canhua

doi:10.1158/0008-5472.22410300.v1

Supplementary Figure S1-2 from Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer

journal contribution

posted on 2023-03-30, 23:53 authored by Qianhui Dou, Hai-Ning Chen, Kui Wang, Kefei Yuan, Yunlong Lei, Kai Li, Jiang Lan, Yan Chen, Zhao Huang, Na Xie, Lu Zhang, Rong Xiang, Edouard C. Nice, Yuquan Wei, Canhua Huang

<p>Supplementary Figure S1-2</p>

Funding

Basic Research Program of China

National Science and Technology Major Project

NSFC

Sichuan Science-Technology Innovative Research Team

History

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DOI - Is supplement to Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer

ARTICLE ABSTRACT

Breast cancer is the most common cancer among women worldwide, yet successful treatment remains a clinical challenge. Ivermectin, a broad-spectrum antiparasitic drug, has recently been characterized as a potential anticancer agent due to observed antitumor effects. However, the molecular mechanisms involved remain poorly understood. Here, we report a role for ivermectin in breast cancer suppression by activating cytostatic autophagy both in vitro and in vivo. Mechanistically, ivermectin-induced autophagy in breast cancer cells is associated with decreased P21-activated kinase 1 (PAK1) expression via the ubiquitination-mediated degradation pathway. The inhibition of PAK1 decreases the phosphorylation level of Akt, resulting in the blockade of the Akt/mTOR signaling pathway. In breast cancer xenografts, the ivermectin-induced cytostatic autophagy leads to suppression of tumor growth. Together, our results provide a molecular basis for the use of ivermectin to inhibit the proliferation of breast cancer cells and indicate that ivermectin is a potential option for the treatment of breast cancer. Cancer Res; 76(15); 4457–69. ©2016 AACR.