Blood Psychic Granules Resistance To Tumor Invasion And Metastasis Mechanisms

The expression of matrix metalloproteinase-9(MMP-9) has been implicated in the invasion and metastasis of cancer cells. We concentrated on the mechanism of inhibitory effect of traditional Chinese formula Hyul-Tong-Ryung EtOAt extract (HE) on the PMA-induced MMP-9 secretion and expression in the human cell lines.Here we found that in zymography assay, HE inhibits the PMA-induced MMP-9 induction in different human cell lines in the non-toxicity concentration. Based on this reason, HE drastically decreased the invasion ability of PMA-induced MCF-7 cells. In order to find out if the inhibitory effect is dues to the amount of protein expression, Western blot was used to detect the MMP-9 protein expression. The results show the same trend as zymograpgy test .These results suggested that the selective inhibitory effect of HE on the PMA induced MMP-9 secretion is correlated with the synthesis of MMP-9 protein.Furturemore as evidenced by MMP-9 promoter, RT-PCR and electrophoretic mobility shift (EMSA) assays, HE significantly and specifically inhibited MMP-9 gene expression by blocking PMA-simulated activation of activator protein-1 (AP-1) which is through the phosphorylated c-Jun the heterodimer protein of AP-1.Study about the regulation of MMP-9 transcription and expression indicated that, gene expression could be activated by MAPK signal transduction pathways including ERK1/2, p38, and JNK, which are the upstream modulators of AP-1 and NF-kB. Our data showed that the activation of ERK1/2 and JNK play the major role in regulating the MMP-9 expression. At the same time, HE dramatically suppressed the phosphorylation of ERK1/2 and partial of JNK, which suggested that HE suppressed PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7.