Aspirin inhibits proliferation and metastasis of canine mammary gland tumor cells through Wnt signaling axis

Background: Breast cancer is one of the most common, lethal types of neoplasia. The high mortality is largely due to rapid growth and distal metastasis. Epithelial-mesenchymal transition (EMT) and increased activity of matrix metalloproteinases (MMPs), which are related to tumor aggressiveness and progression, are known to be essential processes. Aspirin, a classic anti-inflammatory treatment, has been shown to inhibit the different types of cancer, though its research have yet to be elucidated and remain controversial. Methods: We set out to elucidate the mechanism of Aspirin against the metastasis of canine mammary gland tumor cells (CMGTs), and provide theoretical support for the rational use of non-steroidal anti-inflammatory drugs. Firstly, we utilized CCK8, wound healing and transwell invasion assays to determine the effect of Aspirin on proliferation and migration of CMGTs. Next, we determined the effect of Aspirin on Wnt/beta-catenin signaling by cellular immunofluorescence and western blot analysis. Finally, Wnt/beta-catenin pathway activating agent (Wnt3a) and inhibitor (FH535) were utilized to further validate the relationship between Aspirin and Wnt/beta-catenin signaling. Results: The results indicated that Aspirin inhibits proliferation and migration of CMGTs in a time-and concentration-dependent manner. Moreover, the inhibitory effect of Aspirin on CMGTs was reduced upon addition of a Wnt pathway activating agent (Wnt3a), while the effect following the addition of Wnt pathway inhibitor (FH535) remained the same as that of Aspirin. Conclusions: Our study demonstrates that Aspirin can inhibit the proliferation, migration and invasion by inhibiting Wnt/beta-catenin signaling, which suggest it can be a promising tool for deterring metastasis of CMGTs.

Automated summary

The study demonstrates that aspirin can inhibit the proliferation, migration, and invasion of canine mammary gland tumor cells by inhibiting Wnt/β-catenin signaling. This suggests that aspirin could be a promising tool for deterring metastasis of CMGTs.