Dai Jin, Van Wie Peter G, Fai Leonard Yenwong, Kim Donghern, Wang Lei, Poyil Pratheeshkumar, Luo Jia, Zhang Zhuo
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536, USA.
Toxicol Appl Pharmacol. 2016 Nov 15;311:106-112. doi: 10.1016/j.taap.2016.09.016. Epub 2016 Sep 20.
Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression.
芹菜素是一种天然黄酮类化合物，在包括结直肠癌在内的多种癌症中具有多种抗癌特性，如抗增殖、抗炎和抗转移。神经前体细胞表达发育下调基因9（NEDD9）是一种Cas家族的多结构域支架蛋白，已被证明与癌症转移和进展相关。本研究探讨了NEDD9在芹菜素抑制结直肠腺癌DLD1和SW480细胞迁移、侵袭和转移中的作用。结果表明，敲低NEDD9可抑制细胞迁移、侵袭和转移，而NEDD9的过表达则促进DLD1细胞和SW4890细胞的迁移和侵袭。芹菜素处理可在蛋白水平上减弱NEDD9的表达，导致FAK、Src和Akt的磷酸化减少，从而抑制DLD1和SW480细胞的迁移、侵袭和转移。本研究表明，芹菜素通过NEDD9/Src/Akt级联反应抑制结直肠癌细胞的迁移、侵袭和转移。NEDD9可能作为一种生物标志物，用于评估癌症侵袭性和选择抗癌症进展的治疗药物。
