Extracellular Acidity-mediated Expression of cPLA2γ Confers Resistance in Gastric Cancer Cells.

BACKGROUND/AIM: Extracellular acidity, a characteristic of solid tumors, has been proposed to be a critical factor for aggravating tumor malignancy and conferring resistance to therapeutics. Recently, acidity has been implicated in inflammatory responses, which are mediated through active lipid metabolites in various human tissues. In the present study, we investigated whether acidity can affect lipid-mediated signaling, and found that phospholipase A2 (PLA) activity increased at acidic pH in SNU601 and AGS gastric carcinoma cell lines.

MATERIALS AND METHODS

To identify the PLA isoform that is responsible for the acidity-induced activity, we assessed mRNA levels of cPLA isotypes through real-time qPCR, and protein levels through immunoblot assay in cells cultured in acidic medium.

RESULTS

It was found that acidic pH conditions markedly elevated the PLAγ expression. A gene interference study using specific siRNA of cPLAγ suggested that expression of cPLAγ in acidic culture conditions may be associated with protection of cancer cells in acidic environment, as shown by cell viability and clonogenic assays. In addition, expression of cPLAγ appeared to confer cell resistance to anticancer drugs under acidic pH conditions.

CONCLUSION

Acidity-induced cPLAγ expression may exert protective effects by imparting resistance to the gastric cancer cells under acidic environment.