Department of General Surgery, Qingdao University, Qingdao, Shandong, Reople's Republic of China.
Eur Rev Med Pharmacol Sci. 2013 Jul;17(13):1703-8.
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.
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.
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.
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.
背景-目的：在胃癌（GC）中，PLA2G2A 磷脂酶的高表达与患者生存率的提高有关。PLA2G2A 也是 GC 中增殖、侵袭和转移的重要调节因子。然而，尚未有关于 PLA2G2A 与 GC 细胞化疗敏感性的关系的报道。5-氟尿嘧啶（5-FU）广泛用于治疗晚期胃癌。然而，此类患者常对 5-FU 产生耐药性，这种耐药性成为化疗的一个关键问题。这种耐药性的机制在很大程度上尚不清楚。在本研究中，我们研究了 PLA2G2A 是否可以在体外赋予 GC 细胞对 5-FU 的耐药性或增敏性。
通过 MTT 测定法测定 GC 细胞系 SGC-7901、MKN-45、RF-48、N87、AGS、MKN-28、RF-1、MGC-803 的 5-FU 敏感性。通过 Western blot 测定法测定 PLA2G2A 水平。体外测定 5-FU 对 PLA2G2A 表达的影响。通过小干扰 RNA 沉默 PLA2G2A 抑制 PLA2G2A 在体外的表达。通过转染全长 PLA2G2A cDNA 体外过表达 PLA2G2A，并评估对 5-FU 敏感性的影响。
细胞系 SGC-7901、MKN-45、RF-48 和 N87 对 5-FU 敏感，而 AGS、MKN-28、RF-1 和 MGC-803 对 5-FU 耐药。基础 PLA2G2A 与 5-FU 敏感性之间存在显著相关性。沉默 PLA2G2A 增加了 5-FU 处理细胞中的 5-FU 杀伤作用，而过表达 PLA2G2A 降低了 5-FU 处理细胞中的 5-FU 杀伤作用。
PLA2G2A 与 5-FU 敏感性相关。沉默 PLA2G2A 对 5-FU 治疗敏感。因此，PLA2G2A 可能是胃癌亚群的一个有用的治疗靶点。
