Combination therapy with capsaicin and doxorubicin inhibits TNBC metastasis by targeting TGF-beta thereby increasing survival in a 4T1 transplanted murine model.

Aggressive and highly metastatic nature of triple negative breast cancer (TNBC) coupled with its tumor microenvironment renders conventional chemotherapeutics quasi-effective. Despite favourable response to systemic therapy in early stage TNBC, development of metastatic disease within a few years of diagnosis is a common occurrence which indicates the presence of occult metastasis that escaped chemotherapy. TGFβ (transforming growth factor beta) signalling is known to play an important role in TNBC's metastatic aggressiveness. TGFβ inhibitors are being investigated as antimetastatic agents. In vitro studies suggest the potential of Capsiacin as TGFβ inhibitor though in vivo evidences are unexplored. The study explores the use of capsaicin singly or in combination with conventional therapeutics to enhance anti-metastatic effect as well as effective reduction of tumor load. Furthermore, exploration of capsaicin as TGFβ inhibitor in metastatic micro environment was studied. 4T1 transplanted in vivo TNBC murine model was used to access parameters pertaining to tumor growth, metastasis and survival were evaluated at 14, 28 and 42 days following the tumor cell inoculation. Capsaicin in combination with doxorubicin was more effective in reducing primary tumour burden, metastasis, as well as in improving overall survival when compared to treatment with either capsaicin or doxorubicin alone. This therapeutic combination also effectively modulated the tumor microenvironment at the metastatic sites. Capsiacin effectively demonstrated TGFβ inhibition both at primary and metastatic sites and reduced metastasis and improved prognosis. This study highlights the potential of combining capsiacin's anti-metastatic role along with conventional chemotherapeutics in TNBC treatment.