Anti-breast Cancer Effect And Mechanism Of SBFI-26,A Inhibitor Of FABP5

Breast cancer is the most common malignancy in women and the leading cause of deaths worldwide.It is necessary to develop low-toxic drugs for patients.Fatty acid metabolism plays an important role in the survival of tumor cells.What transports fatty acids are substances called fatty acid transporters(FABPs).FABP5 is the fifth member.SBFI-26 is an analog of Incarvillea,which has the function of inhibiting theFABP5 protein.In order to investigate whether this compound has potential therapeutic effect and possible mechanism on breast cancer,this subject has carried out the following three work studies.1.Breast cancer cells were cultured,and the inhibitory effects of SBFI-26 were evaluated by vitro cell experiments.The results showed after treatment with 100 μmol / L SBFI-26,the cell viability of MCF-7,MDA-MB-468 and MDA-MB-231 decreased to 54.00 +0.81%,58.82 + 0.034% and 46.44 + 0.054%,respectively.At this concentration,the migration,invasion and cloning ability of each cell were significantly inhibited.2.Breast cancer tumor model was established and intraperitoneal injection was given for 21 days.Results showed that SBFI-26 had no significant effect on the body weight,high and low doses had a certain inhibitory effect on tumor development.H&E staining results showed that the drug did not damage the main organs.Immunohistochemical results showed that SBFI-26 reduced the expression of VEGF protein in tumors of nude mice.3.Through mmunohistochemistry experiments to explore the molecular mechanism of tumor growth inhibition in vivo.Immunoblot results showed that SBFI-26 could decrease the expression of downstream proteins PPARβ/δ and VEGF.The use of PPARβ/δ agonists demonstrated that SBFI-26 may inhibit the growth of breast cancer cells by inhibiting the FABP5-PPARβ / δ-VEGF pathway.The results of fatty acid uptake experiments show that SBFI-26 can reduce the stimulation of downstream PPARβ/δ signals by inhibiting FABP5 transporting fatty acids,thereby reducing the generation of angiogenic factor VEGF.Conclusion: SBFI-26 can inhibit the proliferation,migration,invasion and cloning of breast cancer cells MCF-7,MDA-MB-468 and MDA-MB-231 in vitro;it can reduce tumor formation and development in vivo.It is speculated that the expression of VEGF may be reduced by inhibiting the FABP5-PPARβ/δ pathway according to immunoblot experiments and the like.This study demonstrates that SBFI-26 has potential for treating breast cancer,providing basic data and references for subsequent drug development.