The Screening And Activity Study For New Anti-tumor Drug

Polo-like kinase 1(Plk1)was a Ser/Thr kinase reported in 1994 by Swiss laboratory cancer institute firstly.It partcipates precise regulation of different checkpoints such as chromosome separation,centrosome maturity,spindle formation,and regulates the cell mitosis.At present,Plkl is found to be overexpressed in malignant cells such as lung cancer,cervical cancer and stomach cancer.Serving as a negative prognostic marker in specific human cancers,Plkl is a promising target for antitumor therapy.To find potential small-molecule Plkl inhibitors,This paper adopts the method of fluorescence polarization targeting Plkl PBD through high throughput screening compound libraries in laboratory research,find one Plkl PBD active compound 6143D7.And adopts MTT?cell cycle?cell apoptosis cell migration(scratch)and molecular virtual docking series of activity research in vitro.Confirmed that the compound 6143D7 can inhibit HeLa?PC3 in different degrees,especially on HeLa cell the IC50 reached 5.786±0.165?M;Flow cytometric analysis found that the compounds 6143D7 could induce the S and G2/M phase arrest in HeLa cells;The Annexin V-PI dyeing and flow cytometric analysis verified that compared to the DMSO control group,the proportion of apoptotic cells increased in a dose dependent manner;Cell migration(scratches)experiment of compound 6143D7 can inhibit HeLa migration ability,and presents in a dose and time dependent manner;Molecular docking showed that 6143D7 has good affinity with the PBD1 domain.The results show that the compound 6143D7 is expected to become one of the anti-cancer drug candidates against Plkl PBD.