The effects of TRKA agonist amitriptyline and TRPV1 modulators alone and in combination in metastatic breast cancer

Objective: Breast cancer is the most diagnosed cancer in women with high mortality rate and the development of metastasis limits the treatment options. It has been shown the expression of TrkA and TRPV1 channels in breast carcinoma in literature. Neuronal studies reported that TrkA reseptor activation increases the TRPV1 channel sentisization. However, there are few studies conducted on the activities of these reseptors alone or in combination in cancer. In this study, the effects of the use of TrkA agonist Amitriptilin and TRPV1 modulators alone or in combination in metastatic breast carcinoma investigated. Method: 67NR, 4T1 and it's substypes 4TBM and 4THM breast carcinoma cell lines were used to identify the expressions of TRPV1 and TrkA with western blot. The effects of TrkA agonist Amitriptilin, TRPV1 agonist Olvanil and TRPV1 antagonist AMG9810 on cell proliferation were investigated with cell culture techniques. The type of the relation between TrkA and TRPV1 in 4TBM and 4THM cell lines were identified with isobologram graph and CI value in cell culture. Results: TRPV1 and TrkA expression were seen in 67NR, 4T1, 4THM and 4TBM cell lines. Amitriptilin, Olvanil and AMG9810 agents supressed cell proliferation in both 4TBM and 4THM cell lines. Amitriptrilin decreased cell proliferation in different doses in combination either Olvanil or AMG9810 and their CI values found either equal to 1 or less then 1. Conclusion: The expression of TrkA was shown for the first time in 67NR, 4T1 and it's subtypes. Different from literature, it has been found that Amitriptilin has antiproliferative effects on breast carcinoma cells. The effects of the interaction between TrkA and TRPV1 on cell proliferation were identified in metastatic breast carcinoma for the first time.