Exploration On The Mechanism Of The Inhibition Effects Of NKL30on Cervical Cancer Cells

Objective:To investigate the mechanism of the inhibition effects of NKL30and its analogues on cervical cancer cellsMethods:Cervical cancer cell Hela were treated with new HDAC inhibitors NKL30and its analogues of different concentrations(5、10、20、40μM) for24h, Hela cell viabilities were measured with CellTiter-Glo Luminescent Cell Viability Assay; Using Hela extracts after treatment of different concentrations of NKL30and its analogues A and B for24h, HDAC activity were measured using HDAC colorimetric assay kit Color deLys (BIOMOL Research Laboratories, Plymouth Meeting, PA); Co-transfection of3×MEF2and β-gal luciferase expression plasmid to Hela to determine MEF2transcription activation; Using Western blot to determine Nur77expression of normal cervical cell Hacat,cervical cancer cell Hela,Caski,C33A after24h treatment of NKL30.Comparing the significant differences of the effects of NKL30and its analogues A and B on Hela cell viability, HDAC activity, MEF2transcription activity and Nur77expression among different concentrations by statistical analysis.Results:1. NKL30and its analogues A and B inhibit cervical cancer cell Hela viabilities;2. NKL30and its analogues A and B displayed mild inhibition effects on HDAC activities without obvious relatonships with concentration gradient;3. NKL30and its analogues A and B enhanced MEF2transcription activity correlating to concentration gradient;4. NKL30stimulated Nur77expression correlating to concentration gradient.Conclusion:1. NKL30and its analogues A and B inhibited cervical cancer cell viabilities;2. Inhibition effects of NKL30and its analogues on cervical cancer cells correlate to its activating MEF2transcription instead of inhibiting HDAC activities.3.The induction of the expression of Nur77by NKL30in the cervical cancer cell lines may be the possible mechanism of inhibiting cancer cells.