The Study On The Inhibition Of The Cancer Cell Migration And Its Mechanism Of Thiazolyl-Pyrazole-Tethered Peptidomimetics

Recent study has shown that the peptide molecules and benzothiazole-pyrazole-AWD*I,could inhibit the migration of tumor cells.Based on the results of this study,the antimigration,anti-invasion,cytotoxicity and mode of action of the analogues of the peptidomimetic was detected.The effect of tumor cells on the compound was tested with a series of bioassays such as wound healing,cell migration?Transwell?experiment,cell invasion,cell toxicity test,cell clone formation experiment,the RT-PCR test,Western blotting,cell immune fluorescence experiments.The results of wound healing assays and Transwell assays showed that the substituent was Br whose ability of cell antimigration was higher than the rest of compounds.When the concentration of the compound with Br?3f?was 5?M,the inhibition rate of breast cancer cell migration and cell anti-invasion was 45.6%(Inhibition of tumor cell migration IC₅₀=5.3?M)and 34.7%.Moreover,in the experiments of cell viability and cell clone formation assasys,the compound did not have significant toxicity and did not have significant effect on cell proliferation.The cell migration experiment was used to test the concentrations of different concentration of compounds 3f influence on the motility of MDA-MB-231 cells.The results showed that increase in concentration of the compounds could increase inhibition effect on cell migration.Furthermore keeping the concentration of the compound 3f,the results showed that with the increase of the concentration of the phospholipase could decrease the inhibition effect on the cell migration.And the compound 3f could inhibit migration of different tumour cells such as MCF-7,A549,HELA.When the concentration of the compound 3f was 5?M,the inhibition rate of MCF-7,A549,HELA was 55%,45%,33%.The result of the reverse transcription PCR and Western experiment showed that compound 3f could decrease the Cofilin expression of RNA and protein.And the cytoskeleton F-actin shows diffuse effects on the compound 3f.Above all,quasi peptide molecular terminal substituent on the benzene ring counterpoint to Br,which can inhibit cell migration,invasion and have no significant toxicity.It also may be affected by the RhoA signalling pathways and regulate Cofilin protein expression.It can be used as the lead compound for further research on drugs.This paper provides a good basis and scientific basis for the development of anti-tumor metastatic drugs.