Journal
SCIENTIFIC REPORTS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep05518
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Funding
- National Natural Science Foundation of China [81370088, 81227802]
- Fundamental Research Funds for the Central Universities of zhuizong
- project of shaanxi star of science and technology [2012KJXX 06]
- supporting plan of education ministry's new century excellent talents [NCET-13-0467]
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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 PKC beta 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 PKC beta, 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, NF kappa B 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.
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