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

D. Chen, X.-l. Jiao, Z.-k. Liu, M.-s. Zhang, M. Niu

Department of General Surgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, R.P. China. chendd820@126.com

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• Oncology

BACKGROUND-AIM: Elevated expression of the PLA2G2A phospholipase in gastric cancer (GC) is associated with improved patient survival. PLA2G2A is also an important regulator of proliferation, invasion and metastasis in GC. However, no relation about PLA2G2A and chemosensitivity in GC cells was reported. 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 resistance becomes a critical problem for chemotherapy. The mechanisms underlying this resistance are largely unknown. In the present study, we investigated whether PLA2G2A could confer 5-FU resistance or sensitise in GC cells in vitro.

MATERIALS AND METHODS: The 5-FU sensitivity of GC cell lines SGC-7901, MKN-45, RF-48, N87, AGS, MKN-28, RF-1, MGC-803 were determined by MTT assays. PLA2G2A levels were determined 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. Significant 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 sensitive to 5-FU treatment. Thus, PLA2G2A may be a useful therapeutic target for a subset of gastric cancers.

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