Abstract
BackgroundMammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge. Ivermectin, a well-known anti-parasitic agent, has been implicated as a potential anticancer agent in various types of human cancer. However, there are no reports evaluating the antitumor effects of ivermectin in canine mammary tumor. Here, we investigated whether ivermectin was able to inhibit canine mammary tumor development and explored the related mechanisms.ResultsIvermectin inhibited the growth of canine mammary tumor cell lines in a dose- and time-dependent manner. The antitumor effects induced by ivermectin were associated with cell cycle arrest at G1 phase via down-regulation of CDK4 and cyclin D1 expression, with no significant induction of apoptosis. Furthermore, significantly reduced β-catenin nuclear translocation was observed after treatment with ivermectin, resulting in the inactivation of WNT signaling. Consistent with the results in vitro, a significant suppression of tumor growth by ivermectin was observed in canine mammary tumor xenografts.ConclusionIvermectin, as a promising anti-cancer agent, inhibits the growth of canine mammary tumor by regulating cell cycle progression and WNT signaling.
Highlights
Mammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge
We found that ivermectin inhibited canine mammary tumor growth by regulating cell cycle progression and the Wingless-type MMTV integration site family (WNT)/β-catenin signalling pathway
Ivermectin inhibits cell proliferation To ascertain the antiproliferative effect of ivermectin in canine mammary cancer, the Cell Counting Kit-8 (CCK-8) assay was used to assess the growth of canine mammary tumor cell lines (CMT7364 and CIPp) following ivermectin treatment
Summary
Mammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge. There are no reports evaluating the antitumor effects of ivermectin in canine mammary tumor. We investigated whether ivermectin was able to inhibit canine mammary tumor development and explored the related mechanisms. Mammary gland tumor (MGT) is the most common tumor in intact female dogs [1], and a higher incidence of malignant MGT in spayed female dogs deserves more attention [2]. Cell proliferation is a natural process regulated by checkpoints, but these regulators are often altered in cancer cells [12].
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