Celastrol Inhibits Canine Mammary Tumor Cells by Inducing Apoptosis via the Caspase Pathway.

Guoxing Ou,Shimin Pei,Xiaolong Li,Xianyu Jiang,Ang Gao,Zijun Lin

doi:10.3389/fvets.2021.801407

Abstract

Canine mammary tumor is a serious disease threatening the health of dogs and can be used as a research model for human breast cancer. The study of canine mammary tumor has a role in improving the welfare of dogs. Most common canine mammary tumor chemotherapy drugs have limited effects and drug resistance. Celastrol is an extract of Tripterygium wilfordii, which has a wide range of biological activities, including significant anti-tumor effects. At present, celastrol has not been used in the clinical treatment for canine mammary tumor. This study investigated the anti-tumor properties of celastrol through in vitro assay of cell proliferation inhibition, cell colony, cell migration, and invasion; flow cytometry, qPCR, and Western Blot methods were used to explore the anti-tumor mechanism of celastrol. The results showed that celastrol can inhibit the proliferation of canine mammary tumor cells in vitro, and decrease the migration and invasion ability of canine mammary tumor cells. We also found that celastrol can upregulate Cleaved Caspase-3 and Cleaved Caspase-9 protein expression levels to promote cell apoptosis, and can regulate cell cycle-related proteins to induce cell cycle arrest. In summary, celastrol may inhibit canine mammary tumor cells through the Caspase pathway, providing a new direction for anti-canine mammary tumor drugs, and is expected to become a new anti-cancer drug for canine mammary tumors.

Highlights

Canine mammary tumor (CMT) is the most common tumor in female dogs, with an incidence of 50–70% of all tumors in intact female dogs, and its recurrence and mortality rates are high [1]
To investigate the inhibition effect of celastrol on canine mammary tumor cells proliferation, the CMT-7364 and CIPp cells were treated with different concentrations of celastrol (0.1, 0.4, 0.8, 1.2, and 1.6 μM)
The above results indicate that celastrol significantly inhibits the proliferation of canine mammary tumor cells

Summary

Introduction

Canine mammary tumor (CMT) is the most common tumor in female dogs, with an incidence of 50–70% of all tumors in intact female dogs, and its recurrence and mortality rates are high [1]. Accurate diagnosis, effective treatment, and reasonable prognosis of canine mammary tumors are of great significance for maintaining the health of dogs. A large number of studies have shown that CMT and HBC are similar in many aspects, including molecular, histology, morphology, genetics, clinical, and epigenetics [3,4,5]. Since the living environment of pet dogs is similar to that of humans, spontaneously formed CMT can be used as a good model for the study of human breast cancer, which is conducive to the promotion of comparative studies on the prognosis and treatment of breast cancer

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Conclusion