β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine in�vitro and in�vivo

Abstract

Abstract. The present study aimed to determine the anticancer effects of the combination of β-elemene and ligustrazine in vitro as well as in in vivo. Following evaluation using an MTT assay, β-elemene, ligustrazine and the β-elemene-ligustrazine combination treatments all exhibited the capacity to inhibit the growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%, respectively. Using a flow cytometry assay, it was determined that the β-elemene-ligustrazine combination possessed the highest apoptotic rate (30.6%). Furthermore, β-elemene-ligustrazine combination treatment resulted in the highest downregulation of G protein-coupled receptor 124, vascular endothelial growth factor, matrix metallopeptidase (MMP)-2 and MMP-9 mRNA, and protein expression levels. In addition, the combined treatment led to an increase in the mRNA and protein expression of endostatin, TIMP metallopeptidase inhibitor (TIMP)-1 and TIMP-2 in OS-732 cells. Additionally, β-elemene-ligustrazine caused a decrease in nuclear factor-κB, interleukin-8, C-X-C motif chemokine receptor 4 and urokinase-type plasminogen activator mRNA expression, as well as an increase in caspase-3, caspase-8, and caspase-9 mRNA expression. In vivo, the β-elemene-ligustrazine combination was able to reduce the weight and the bulk of the tumor in BALB/c-nu/nu nude mice compared with any other group. All the results described above regarding changes to mRNA and protein expression were further confirmed in vivo in the tumor tissue of mice. The results of the present study have suggested that the combination of β-elemene-ligustrazine exhibits greater anticancer effects compared with β-elemeneor ligustrazine-alone treatment.

Anti-endometriosis Mechanism of Jiawei Foshou San Based on Network Pharmacology

“…Ligustrazine from L. chuanxiong Hort, ferulic acid from A. sinensis , and tetrahydropalmatine are mixed to JFS with the certain proportion. Firstly, in previous study, ligustrazine has the anti-metastatic effects through decreasing MMP-2, MMP-9, MMP-3, MMP-13, increasing TIMP-1, TIMP-2 ( Liang et al, 2014 ; Jiang et al, 2017 ; Fang et al, 2018 ). But up-regulating expression of MMP-2 and MMP-9 is found in bone marrow mesenchymal stem cells by ligustrazine ( Wang et al, 2016 ).…”

Combination of ferulic acid, ligustrazine and tetrahydropalmatine inhibits invasion and metastasis through MMP/TIMP signaling in endometriosis

“…However, these three ingredients processed equivocal reaction on MMP/TIMP signaling. On one hand, metastatic suppression is found in three ingredients in various kinds of cancer, for example osteosarcoma, fibrosacroma, and breast cancer ( Fang et al, 2018 ; Yodkeeree et al, 2013 ; Zhang et al, 2016 ). Especially, ferulic acid and ligustrazine show downregulation of MMP-2/9, and upregulation of TIMP-1 ( Fahrioglu et al, 2016 ; Fang et al, 2013 ; Xu et al, 2018 ; Yue et al, 2019 ).…”

Inhibition of Jiawei Foshou San on invasion and metastasis through MMP/TIMP signaling in endometriosis

“…Whether activating blood and dissolving stasis mean inhibit invasion and metastasis or not will depend on individual situations. On one hand, the suppression of metastatic potential is found in ligustrazine, ferulic acid, or tetrahydropalmatine in various kinds of cancer, for example osteosarcoma, brosacroma, and breast cancer [14][15][16]. Especially, ligustrazine shows downregulation of MMP-2/9, and upregulation of TIMP-1.…”