Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1854
Peer-review started: February 21, 2019
First decision: March 5, 2019
Revised: March 10, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: April 21, 2019
As one of the most frequent cancers, gastric cancer caused more than 700,000 deaths in just 2012 worldwide. Although 5-ﬂuorouracil (5-Fu) is often employed as treatment against gastric cancer, its effect is severely affected by drug resistance of gastric cancer cells. Cycas revoluta Thunb. Extract has shown promise as a cancer treatment, though its effect on gastric cancer remains unknown.
To find new ways for chemical sensitization of cancer cells and improve the effect of 5-Fu during chemotherapy against malignancies.
To explore the anti-cancer effect of Cycas revoluta Thunb. in gastric cancer and investigate its chemical sensitization effect against gastric cancer cells during 5-Fu treatment.
The half-maximal effective concentration and the half-maximal lethal concentration of drugs were determined by cell viability test. The effect of Cycas revoluta Thunb. on gastric cancer cell migration was investigated by wound-healing and transwell assay. The synergistic effect between Cycas revoluta Thunb. and 5-Fu was confirmed by clonogenic assay and apoptosis detection. The expression of crucial proteins was measured by western blotting.
We found that the natural extract of Cycas revoluta Thunb. Preferentially killed gastric cancer cells compared to normal gastric cells. In addition, the extract significantly inhibited gastric cancer cell growth, migration and invasion. Cycas revoluta Thunb. can also improve the inhibitory effects of 5-Fu and effectively induce cell apoptosis. Western blotting analysis showed that P-glycoprotein, p-AKT and mammalian target of rapamycin (mTOR) expression markedly decreased, suggesting that AKT-mTOR pathway plays an important role in chemical sensitization induced by Cycas revoluta Thunb.
Our study demonstrated that the natural extract of Cycas revoluta Thunb. can significantly inhibit gastric cancer cell growth, migration and invasion. Furthermore, it can also improve the effect of 5-Fu and promote apoptosis during chemotherapy. Therefore, our study provides a new drug for improving the clinical effect of chemotherapy in gastric cancer. Our study also showed that Cycas revoluta Thunb. Enhanced the effects of 5-Fu through the AKT-mTOR pathway, offering a novel mechanism for the chemical sensitization effect of Cycas revoluta Thunb.
In the future, research may reveal the main component of Cycas revoluta Thunb. that enhances the sensitivity of cancer cells and further develop for its application in anti-cancer treatments. The identification of the molecular pathway related to AKT-mTOR may further explain the underlying mechanism.