Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis with survival of less than 5 years when advanced. Several studies showed that the ivermectin has antitumor effects on a variety of cancer cells. The present study represents the first study evaluating the anticancer efficacy of ivermectin in pancreatic cancer. We found that the anticancer effect of ivermectin in combination with gemcitabine on pancreatic cancer is more effective than gemcitabine alone. Ivermectin-gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by down-regulated cyclin D1 expression through mTOR/STAT3 signaling pathway. In addition, ivermectin-gemcitabine induced apoptosis by ROS generation and reduction of mitochondrial membrane potential (MMP), and blocked mitophagy. In vivo experiments also confirmed that ivermectin-gemcitabine groups significantly suppressed the tumor growth of pancreatic cancer compared with gemcitabine alone groups. These results indicate that ivermectin has a synergistic effect with gemcitabine in preventing cancer progression and could be a potential antitumor drug for the treatment of pancreatic cancer. 

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Ivermectin, a potential anticancer drug derived from an antiparasitic drug

https://doi.org/10.1016/j.phrs.2020.105207Get rights and content

Highlights

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    Ivermectin effectively suppresses the proliferation and metastasis of cancer cells and promotes cancer cell death at doses that are nontoxic to normal cells.

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    Ivermectin shows excellent efficacy against conventional chemotherapy drug-resistant cancer cells and reverses multidrug resistance.

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    Ivermectin combined with other chemotherapy drugs or targeted drugs has powerful effects on cancer.

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    The structure of crosstalk centered on PAK1 kinase reveals the mechanism by which ivermectin regulates multiple signaling pathways.

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    Ivermectin has been used to treat parasitic diseases in humans for many years and can quickly enter clinical trials for the treatment of tumors.

Abstract

Ivermectin is a macrolide antiparasitic drug with a 16-membered ring that is widely used for the treatment of many parasitic diseases such as river blindness, elephantiasis and scabies. Satoshi ōmura and William C. Campbell won the 2015 Nobel Prize in Physiology or Medicine for the discovery of the excellent efficacy of ivermectin against parasitic diseases. Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways. This suggests that ivermectin may be an anticancer drug with great potential. Here, we reviewed the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death and discussed the prospects for the clinical application of ivermectin as an anticancer drug for neoplasm therapy.