Postbiotics + standard chemotherapy against gastric cancer cells : future combination therapy?

![CDATA[Objective: Gastric cancer is the third leading cause of cancer-related deaths globally. We recently demonstrated that gut microbial metabolites (postbiotics), especially short-chain fatty acids (SCFAs), confer antiproliferative effects against gastric cancer cells. The aims of this study are to a) evaluate the interaction among the SCFAs and b) decipher their potential synergy with standard chemotherapy against the AGS gastric adenocarcinoma cells in vitro. Methods: The antiproliferative effects of three SCFAs- acetate (A), butyrate (B) and propionate (P) against the AGS cells was determined using the Alamar Blue assay. The potential synergy among these SCFAs and their interactions with standard chemotherapy- dexamethasone (D) and doxorubicin (Do) against the AGS cells were quantified using the combination index (CI) model. Furthermore, the molecular mechanisms of action of the SCFAs combinations with standard chemotherapy were elucidated using flow cytometry, reactive oxygen species (ROS) and anti-inflammatory analyses. Results: All three SCFAs and their combinations exhibited significant antiproliferative activity against the AGS cells. The SCFAs also displayed strong synergistic interactions with D and Do (CI values <1; Figure 1). The flow cytometry, anti-inflammatory and ROS analyses also revealed the potential molecular mechanisms of action of the SCFAs in combination with D and Do. Conclusions: The findings of this study underlined the interactions among the SCFAs against gastric adenocarcinoma cancer cells and their potential implementation as combination therapies with dexamethasone and doxorubicin in the future. Further in vivo studies are warranted to validate these findings.]]