Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer

Cancer Res. 2016 Aug 1;76(15):4457-69. doi: 10.1158/0008-5472.CAN-15-2887. Epub 2016 Jun 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / administration & dosage
  • Antiparasitic Agents / pharmacology
  • Antiparasitic Agents / therapeutic use*
  • Autophagy
  • Cell Line, Tumor
  • Female
  • Humans
  • Ivermectin / administration & dosage
  • Ivermectin / pharmacology
  • Ivermectin / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, SCID
  • p21-Activated Kinases / genetics*
  • p21-Activated Kinases / metabolism


  • Antiparasitic Agents
  • Ivermectin
  • PAK1 protein, human
  • p21-Activated Kinases