Study On The Function And Mechanism Of Pyrrolo[3,4b]-quinolin-9-amine Compound FZU-0038-056 In Triple Negative Breast Cancer

Objective:The pyrrolo[3,4b]-quinoline-9-amine compound is a novel compound synthesized by tetrahydro-β-carboline,and its research in tumors has not been reported.This study was to investigate the function and mechanism of pyrrolo[3,4b]-quinoline-9-amine FZU-0038-056 in triple-negative breast cancer,and to evaluate whether FZU-0038-056 can be used as a candidate compound for the treatment of triple-negative breast cancer.Methods:1.Cell resuscitation,culture and cryopreservation;2.Sulfonhodamine B staining(SRB)was used to test cell growth;3.Flow cytometry was used to analyze the effect of compound FZU-0038-056 on triple-negative breast cancer cell cycle and apoptosis;4.Western blot was used to detect the cell cycle and apoptosis-related proteins;5.Lentiviral infection to construct a stable cell line;6.The inhibitory effect of compound FZU-0038-056 on triple-negative breast cancer in vivo was tested by nude mice tumor formation test,and the toxic side effects of the drug were analyzed.Results:1.Compound FZU-0038-056 inhibits triple-negative breast cancer cell survival;2.Compound FZU-0038-056 blocks the triple-negative breast cancer cell cycle G0/G1 phase;3.Compound FZU-0038-056 induced apoptosis of triple-negative breast cancer cells;4.Compound FZU-0038-056 activates P38 MAPK signaling pathway;5.Compound FZU-0038-056 activates the mitochondrial apoptotic pathway of triple-negative breast cancer cells;6.Compound FZU-0038-056 inhibited the growth of HCC1806 xenografts in nude mice,but not affect mouse body weight..Conclusions:1.It was first discovered that pyrrolo[3,4b]-quinoline-9-amine compound FZU-0038-056 can inhibit the survival of triple negative breast cancer cells.2.Compound FZU-0038-056 promotes apoptosis of triple negative breast cancer cell lines by activating the mitochondrial apoptosis pathway.3.Compound FZU-0038-056 inhibits triple-negative breast cancer tumor growth in vivo.