Background The mortality of ovarian cancer ranks the first among female reproductive malignancies, and new drugs need to be explored to improve its prognosis. In recent years, many studies have reported germacrone has anti-tumor effect.
Objective To investigate the effect of germacrone on the proliferation, migration and invasion of ovarian cancer SKOV3 cells and explore its mechanism.
Methods Human ovarian cancer SKOV3 cells were cultured and treated with germacrone at 0, 70, 140, 210, 280 and 350 μmol/L for 24 h, 48 h and 72 h, respectively. The effect of germacrone on the proliferation of ovarian cancer SKOV3 cells was detected by CCK-8 assay. Cell scratch assay and Transwell assay were used to observe the effect of germacrone on the migration and invasion ability of ovarian cancer SKOV3 cells. The expressions of JAK2/STAT3 signaling pathway related proteins and tumor invasion and metastasis related proteins MMP2 and MMP9 in each group were detected by Western Blot.
Results CCK-8 assay showed that germacrone could inhibit the proliferation of SKOV3 cells in a concentration- and time-dependent manner. Cell scratch assay showed that the scratch healing rate of 0 μmol/L, 140 μmol/L, 280 μmol/L germacrone groups were 69.00% ± 6.76%, 40.33% ± 5.21%, 13.79% ± 9.23%, respectively. Transwell migration experiment showed that the number of cells passing through the chamber in 0 μmol/L, 140 μmol/L, 280 μmol/L germacrone groups were 466.5 ± 47.7, 319.4 ± 41.2, 149.7 ± 26.3, respectively. Transwell invasion experiment showed that the number of cells passing through the chamber in 0 μmol/L, 140 mmol/L, 280 mmol/L germacrone groups were 278.6 ± 71.7, 161.0 ± 35.4, 70.1 ± 24.9, respectively. Compared to control group, germacrone groups inhibited the migration and invasion of SKOV3 cells significantly in a concentration-dependent manner (P＜0.05). Western blot results showed that germacrone could dose-dependently down-regulate the protein expressions of p-JAK2 and p-STAT3, decrease p-JAK2/JAK2 and p-STAT3/STAT3, and down-regulate the protein expressions of MMP2 and MMP9 (P＜0.05).
Conclusion Germacrone could inhibit the proliferation, migration and invasion of ovarian cancer SKOV3 cells, and its mechanism may be related to the down-regulation of the activity of JAK2/STAT3 signaling pathway and down-regulation of the expressions of MMP2 and MMP9 protein.
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