Purpose: Traditional Chinese medicine (TCM) has gained increasing attention for the treatment of multiple chronic diseases, such as cancer. Here we aim to identify the antitumor activity of Sichong formula, a novel TCM, in human gastric cancer cells and investigate the underlying mechanisms.
Methods: The AGS and MKN45 gastric cancer cells were treated with Sichong formula at different concentrations. The proliferation rates were tested by CCK-8 and colony formation assays. Cell migration and invasion were tested by scratch and transwell assays. Gelatin zymography was used to detect the matrix metalloproteinase 9 (MMP9) activity in cell suspendents. Cell apoptosis was analyzed by Annexin V/PI staining and flow cytometry. The expression of interest proteins was tested by Western blot.
Results: Cell proliferation analysis indicated that Sichong formula inhibited cell viability of AGS and MKN45 cells in a dose- and time-dependent manner. The IC50 values were 240 μg/mL and 200 μg/mL for AGS and MKN45 cells, respectively. Furthermore, we found that Sichong formula could inhibit the invasion and migration of gastric cancer cells, which might be mediated by the downregulation of MMP9 activity. Flow cytometry results indicated that Sichong formula induced apoptosis in gastric cancer cells through upregulation of Bax/Bcl2 ratio and activation of caspase cascade. The results from Western blot indicated that Sichong formula resulted in cell autophagy and inactivation of AKT signaling pathway.
Conclusion: Our data suggest that Sichong formula inhibits the proliferation and migration and induces apoptosis in human gastric cancer cells. The inhibitory effect of Sichong formula was, at least partly, mediated by cell autophagy and AKT pathway.
Keywords: apoptosis, invasion, migration, MMP9