Breast cancer is the most commonly diagnosed cancer that affects mainly women. Triple-negative breast cancer (TNBC) is the most aggressive type of this disease and remains a challenging problem, mainly due to the lack of targeted therapies. In addition to standard therapies, patients often resort to alternative forms of treatment, especially cannabinoids, but the impact of cannabinoids on the therapy is underexplored. Previous work in Dr. Fon Tacer’s lab shown that γKlotho protein is highly expressed in a subset of TNBC patients, required for TNBC cell survival and therapy resistance. With our work we aimed to investigate the impact of γKlotho and cannabinoids on the response to chemotherapy. First, we examined publicly available databases and performed real-time PCR analysis to determine mRNA expression of Klotho and CNR proteins in different breast cancer tumor types and cell lines. Next, we treated the cells that express γKlotho or control vector with chemotherapeutic doxorubicin and cannabidiol or their combination. We confirmed that cells expressing γKlotho are more resistant to doxorubicin treatment compared to control cells. Further, we showed that cannabidiol also inhibited growth of TNBC cells and importantly increased the efficacy of doxorubicin. Finally, we found that canine mammary tumor cells, which have molecular and histological similarities to TNBC and are the most common form of tumors in non-sterilized dogs, responded similarly to doxorubicin and cannabidiol. Our preliminary research thus further shows that they represent an interesting preclinical model for this aggressive form of breast cancer.
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