Knockdown of PLA2G2A sensitizes gastric cancer cells to 5-FU in vitro

BACKGROUND-AIM: Elevated ex - pression of the PLA2G2A phospholipase in gastric cancer (GC) is associated with improved patient survival.PLA2G2Aisalsoanimportantregulatorof proliferation, invasion and metastasis in GC. How - ever, no relation about PLA2G2A and chemosensi- tivityinGCcellswasreported.5-Fluorouracil(5-FU) is widely used for treatment of advanced gastric cancer. However, it is common for such patients to develop resistance to 5-FU, and this drug resis - tancebecomesacriticalproblemforchemotherapy. The mechanisms underlying this resistance are largely unknown. In the present study, we investi- gated whether PLA2G2A could confer 5-FU resis - tanceorsensitiseinGCcells in vitro . MATERIALS AND METHODS: The 5-FU sensi- tivity of GC cell lines SGC-7901, MKN-45, RF-48, N87, AGS, MKN-28, RF-1, MGC-803 were deter - mined by MTT assays. PLA2G2A levels were de - termined by western blot assays. The effects of 5- FU on PLA2G2A expression were determined in vitro . PLA2G2A was inhibited by silencing of the PLA2G2A using small interfering RNA in vitro . PLA2G2A was overexpressed by transfection of full-long PLA2G2A cDNA in vitro , and the effects were evaluated on 5-FU sensitivity. RESULTS: The cell lines SGC-7901, MKN-45, RF- 48 and N87 were sensitive, whereas AGS, MKN-28, RF-1 and MGC-803 were resistant to 5-FU. Signifi- cant correlation was observed between basal PLA2G2A and 5-FU sensitivity. Silencing of PLA2G2A increased 5-FU killing in 5-FU-treated cells, and overexpression of PLA2G2A decreased 5-FU killing in 5-FU-treated cells. CONCLUSIONS: PLA2G2A was correlated with sensitivity to 5-FU. Silencing of PLA2G2A was sen - sitive to 5-FU treatment. Thus, PLA2G2A may be a useful therapeutic target for a subset of gastric cancers.