Xiu Yin-Ling, Zhao Yang, Gou Wen-Feng, Chen Shuo, Takano Yasuo, Zheng Hua-Chuan
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, P.R. China.
PLoS One. 2014 Jun 12;9(6):e99361. doi: 10.1371/journal.pone.0099361. eCollection 2014.
Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid homologs. Certain antitumor activities of AA have been reported in a variety of cancers. However, the function of AA in ovarian cancer, to date, has remained unknown.
Ovarian cancer cell lines were exposed to AA, after which cell proliferation, apoptosis, invasion and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to assess the mRNA and protein expression levels of Phosphatidylinositol 3-kinase (PI3K), vascular endothelial growth factor (VEGF) and caspase 3.
Our results showed that AA promotes ovarian cancer cell proliferation, inhibits late apoptosis, and induces cell migration and invasion, as well as lamellipodia formation. AA exposure significantly up-regulated PI3K and VEGF mRNA and protein expression, while, in contrast, it down-regulated caspase 3 mRNA and protein expression in comparison to untreated control cells.
Taken together, our results demonstrate for the first time that AA may potentiate the proliferation, invasion, metastasis and lamellipodia formation in ovarian cancer cell lines via PI3K, VEGF and caspase 3 pathways.
漆树酸(AA)是2-羟基-6-烷基苯甲酸同系物的混合物。已报道AA在多种癌症中具有某些抗肿瘤活性。然而,迄今为止,AA在卵巢癌中的作用仍不清楚。
将卵巢癌细胞系暴露于AA中,然后进行细胞增殖、凋亡、侵袭和迁移试验。用鬼笔环肽染色观察片状伪足的形成。采用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法评估磷脂酰肌醇3-激酶(PI3K)、血管内皮生长因子(VEGF)和半胱天冬酶3的mRNA和蛋白表达水平。
我们的结果表明,AA促进卵巢癌细胞增殖,抑制晚期凋亡,并诱导细胞迁移和侵袭以及片状伪足形成。与未处理的对照细胞相比,暴露于AA显著上调PI3K和VEGF的mRNA和蛋白表达,而与之相反,下调半胱天冬酶3的mRNA和蛋白表达。
综上所述,我们的结果首次证明AA可能通过PI3K、VEGF和半胱天冬酶3途径增强卵巢癌细胞系的增殖、侵袭、转移和片状伪足形成。