Lou Lianqing, Chen Yong Xin, Jin Lingzhen, Li Xiaofei, Tao Xingfei, Zhu Jinhong, Chen Xiangyi, Wu Shuang, Ye Weiwei, He Jinke, Ding Guoqiang
Department of Infectious Diseases, The Affiliated Yiwu Hospital of Wenzhou Medical College, Zhejiang Yiwu, China.
J Int Med Res. 2013 Feb;41(1):55-63. doi: 10.1177/0300060512474124. Epub 2013 Jan 23.
Lysophosphatidic acid (LPA) is a bioactive lipid mediator involved in tumour progression, cell invasion and metastasis. The mechanism of action of LPA in the invasive and metastatic capacity of human hepatocellular carcinoma (HCC) is not fully understood. This study investigated the effects of LPA on HCC cell invasion and induction of matrix metalloproteinase (MMP) -2 and -9.
LPA receptor levels in HCC cell lines were detected by Western blot analysis; HCC cell invasion was analysed by the Transwell® system. The LPA receptor blocker Ki16425 was used to determine whether HCC cell invasion was LPA dependent. Expression of the MMP2 and MMP9 genes in HCC cells was determined by real-time quantitative reverse transcription-polymerase chain reaction (qPCR).
LPA increased HCC cell invasion, which was LPA-receptor dependent. Real-time RT-qPCR showed that LPA increased MMP9, but not MMP2, expression in HCC cells. Pharmacological inhibition of LPA receptors with Ki16452 significantly attenuated LPA-induced HCC cell invasion.
HCC invasiveness is facilitated by LPA and may be relevant to tumour progression. Thus, LPA receptors may be a potential therapeutic target for HCC.
溶血磷脂酸（LPA）是一种参与肿瘤进展、细胞侵袭和转移的生物活性脂质介质。LPA在人肝细胞癌（HCC）侵袭和转移能力中的作用机制尚未完全明确。本研究调查了LPA对HCC细胞侵袭以及基质金属蛋白酶（MMP）-2和-9诱导的影响。
通过蛋白质免疫印迹分析检测HCC细胞系中的LPA受体水平；采用Transwell®系统分析HCC细胞侵袭情况。使用LPA受体阻滞剂Ki16425来确定HCC细胞侵袭是否依赖于LPA。通过实时定量逆转录-聚合酶链反应（qPCR）测定HCC细胞中MMP2和MMP9基因的表达。
LPA增加了HCC细胞的侵袭，这是LPA受体依赖性的。实时RT-qPCR显示，LPA增加了HCC细胞中MMP9的表达，但未增加MMP2的表达。用Ki16452对LPA受体进行药理抑制可显著减弱LPA诱导的HCC细胞侵袭。
LPA促进了HCC的侵袭性，可能与肿瘤进展相关。因此，LPA受体可能是HCC的一个潜在治疗靶点。
