Zhang Yanmin, Zhan Yingzhuan, Zhang Dongdong, Dai Bingling, Ma Weina, Qi Junpeng, Liu Rui, He Langchong
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China.
Sci Rep. 2014 Jul 1;4:5518. doi: 10.1038/srep05518.
Tumor growth and metastasis are responsible for most cancer patients' deaths. Here, we report that eupolyphaga sinensis walker has an essential role in resisting hepatocellular carcinoma growth and metastasis. Compared with proliferation, colony formation, transwell assay and transplantable tumor in nude mouse in vitro and vivo, eupolyphaga sinensis walker extract (ESWE) showed good inhibition on the SMMC-7721 cell growth and metastasis. Using genome-wide microarray analysis, we found the down-regulated growth and metastasis factors, and selected down-regulated genes were confirmed by real-time PCR. Knockdown of a checkpoint PKCβ by siRNA significantly attenuated tumor inhibition and metastasis effects of ESWE. Moreover, our results indicate ESWE inhibits HCC growth by not only downregulating the signaling of PKCβ, Akt, m-TOR, Erk1/2, MEK-2, Raf and JNK-1, but also increasing cyclin D1 protein levels and decreasing amount of cyclin E, cyclin B1 and cdc2 of the cycle proteins. At the same time, ESWE reduced MMP2, MMP9 and CXCR4, PLG, NFκB and P53 activities. Overall, our studies demonstrate that ESWE is a key factor in growth and metastasis signaling inhibitor targeting the PKC, AKT, MAPK signaling and related metastasis signaling, having potential in cancer therapy.
肿瘤生长和转移是导致大多数癌症患者死亡的原因。在此，我们报告中华真地鳖在抵抗肝细胞癌生长和转移方面具有重要作用。与体外和体内的增殖、集落形成、Transwell实验以及裸鼠移植瘤相比，中华真地鳖提取物（ESWE）对SMMC - 7721细胞的生长和转移显示出良好的抑制作用。通过全基因组微阵列分析，我们发现了下调的生长和转移因子，并且通过实时PCR对所选的下调基因进行了确认。用小干扰RNA敲低检查点蛋白激酶Cβ（PKCβ）可显著减弱ESWE的肿瘤抑制和转移作用。此外，我们的结果表明，ESWE不仅通过下调PKCβ、Akt、m - TOR、Erk1/2、MEK - 2、Raf和JNK - 1的信号传导来抑制肝癌生长，还通过增加细胞周期蛋白D1的蛋白水平以及降低细胞周期蛋白E、细胞周期蛋白B1和细胞周期蛋白依赖性激酶2（cdc2）的量来实现。同时，ESWE降低了基质金属蛋白酶2（MMP2）、基质金属蛋白酶9（MMP9）以及趋化因子受体4（CXCR4）、纤溶酶原（PLG）、核因子κB（NFκB）和P53的活性。总体而言，我们的研究表明ESWE是一种针对PKC、AKT、丝裂原活化蛋白激酶（MAPK）信号传导及相关转移信号传导的生长和转移信号抑制剂的关键因子，在癌症治疗中具有潜力。
