Wang Kui, Gao Wei, Dou Qianhui, Chen Haining, Li Qifu, Nice Edouard C, Huang Canhua
a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , China.
b Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education and Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China.
Autophagy. 2016 Dec;12(12):2498-2499. doi: 10.1080/15548627.2016.1231494. Epub 2016 Sep 22.
Ivermectin is a broad-spectrum antiparasitic drug that has recently been demonstrated to exhibit potent anticancer activity against colon cancer, ovarian cancer, melanoma and leukemia. However, the molecular mechanism underlying this anticancer effect remains poorly understood. We recently found that ivermectin markedly inhibits the growth of breast cancer cells by stimulating cytostatic macroautophagy/autophagy in vitro and in vivo. Ivermectin inhibits the AKT-MTOR signaling pathway by promoting ubiquitination-mediated degradation of PAK1 (p21 [RAC1] activated kinase 1), leading to increased autophagic flux. Together, our work unravels the molecular mechanism underpinning ivermectin-induced cytostatic autophagy in breast cancer, and characterizes ivermectin as a potential therapeutic option for breast cancer treatment.
伊维菌素是一种广谱抗寄生虫药物，最近已被证明对结肠癌、卵巢癌、黑色素瘤和白血病具有强大的抗癌活性。然而，这种抗癌作用背后的分子机制仍知之甚少。我们最近发现，伊维菌素在体外和体内通过刺激细胞静止性巨自噬/自噬显著抑制乳腺癌细胞的生长。伊维菌素通过促进泛素化介导的PAK1（p21[RAC1]激活激酶1）降解来抑制AKT-MTOR信号通路，导致自噬通量增加。总之，我们的工作揭示了伊维菌素诱导乳腺癌细胞静止性自噬的分子机制，并将伊维菌素表征为乳腺癌治疗的潜在治疗选择。
