Polyphyllin I directly targets stat3 to inhibit proliferation of glioma U251 cells and induce apoptosis / 肿瘤

ABSTRACT

Objective: To investigate the molecular mechanism of polyphyllin (PP) inhibiting proliferation and inducing apoptosis of human gl i oma U251 cel l s by di rectl y targeti ng si gnal transducer and activator of transcription 3 (STAT3). Methods: U251 cells were treated with different concentrations of PP, then the effect of PP on the proliferation of glioma U251 cells was detected by MTT assay, trypan blue dyeing and clone forming assay, respectively. Apoptosis of glioma U251 cells was determined by flow cytometry after Annexin-FITC/PI double staining. The change of mitochondrial membrane potential was detected by flow cytometry after fluorescent probe JC-1 staining. SwissTargetPrediction online prediction software was used to detect the targeting proteins of PP. Western blotting was used to detect the expressions of STAT3 signaling pathway-related proteins. Molecular docking simulated the binding and action modes of PP and STAT3. Results: PPinhibited the proliferation of U251 cells in a time and concentration-dependent manner (all P 0.05). The hydrogen atom of PP was capable of forming hydrogen bonds with the oxygen atom of aspartic acid (Asp)-334 on STAT3, thereby enhancing its ability of targeting STAT3. Conclusion: PP can inhibit the proliferation of glioma U251 cells and induce apoptosis by directly targeting STAT3.