Anti-Tumor Effect and Mechanism of Parthenolide in Gastric Cancer Cellline BGC-823

Abstract

Objective: To study the anti-tumor effect and mechanism of parthenolide in gastric cancer cell BGC-823. Methods: The cck8 assay was used to detect the changes of BGC-823 cells viability after treatment with different concentrations of parthenolide at different time points. The proliferation ability of BGC-823 cells was detected by clone formation assay. And the cell cycle and apoptosis were measured by flow cytometry. Meanwhile, to detect the difference in intracellular ROS production levels, the fluorescence assay was used. And with the help of western blotting, cell cycle-and apoptosis-related protein expression can be detected. Results: Parthenolide could inhibit the viability of BGC-823 cells in a dose-and time-dependent manner (P < 0.01). In BGC-823 cells exposed to parthenolide, the apoptosis rate was found significantly increased (P < 0.01), and the protein expression of cleaved-caspase3, cleaved-caspase8, and cleaved-caspase9 significantly increased (P < 0.01); the cell cycle was arrested at G1phase (P < 0.01); the protein levels of CyclinD1 and CyclinE1 decreased (P < 0.01), and the expression of P53 and P21 protein increased (P < 0.01); massive intracellular ROS generation was found (P < 0.01). Furthermore, the nuclear protein levels of c-Myc, E2F1, and NF-κB and the protein level of phosphorylated STAT3 decreased in BGC-823 cells exposed to parthenolide (P < 0.01). Conclusion: Parthenolide may inhibit the proliferation of BGC-823 cells and induce G1-phase cell cycle arrest and apoptosis via inhibiting STAT3-c-Myc-E2F1 axis.