[Effect of genistein on MAPK signal pathway in the collagen-induced arthritis fibroblast-like synoviocytes].

OBJECTIVE: To study the effect of genistein (Gen) on MAPK signal pathway in the CIA rat fibroblast-like synoviocytes (FLS). METHODS: The rat model of collagen-induced arthritis (CIA) was established. The cultured FLS of CIA rats were divided using randomized method. The effects of Gen (at the concentration of 50, 100, and 200 micromol/L, respectively) on the proliferation of FLS in CIA rats using methyl thiazolyl tetrazolium (MTT) assay. Effects of Gen (at the concentration of 50, 100, and 200 pmol/L, respectively) on the expressions of extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) in the FLS of CIA rats were detected. RESULTS: Gen could inhibit the proliferation of FLS in CIA rats. The FLS proliferation in the high dose Gen group at 72 h was only 1.10+/-0.04, significantly lower than that in the model group (2.12+/-0.03, P<0.01). Besides, after Gen's action on FLS, the expression of p-ERK was down-regulated. It was only 0.34+/-0.02 in the high dose Gen group, significantly lower than that in the model group (2.68+/-0.14, P<0.01). There was no change in the expression of ERK (P>0.05). CONCLUSIONS: Gen could inhibit the proliferation of FLS in CIA rats. Its mechanism of action was mainly correlated to down-regulating the tyrosine kinase of MAPK signal transduction pathway and inhibiting phosphorylation of ERK.

[Effects of arsenic trioxide on expressions of vascular endothelial growth factor and P-glycoprotein in multidrug resistant leukemia cell line K562/A02].

OBJECTIVE: To investigate the effects of arsenic trioxide (ATO) on the expressions of vascular endothelial growth factor (VEGF) and P-glycoprotein (P-gp) in K562/A02 cells and to explore the correlation between VEGF and P-gp. METHODS: The inhibition rate of K562/A02 cell proliferation was detected by using methyl thiazolyl tetrazolium assay (MTT); the level of VEGF was detected by enzyme-linked immunosorbent assay (ELISA) and the expression rate of P-gp was determined by flow cytometry (FCM). RESULTS: 0.05 micromol/L ATO had no influences on the cell proliferation and the expression of VEGF in K562/A02 cells; 0.4 and 3.2 micromol/L ATO could significantly inhibit the K562/A02 cell proliferation and down-regulate the expression of VEGF in K562/A02 cells (P<0.05). The expression of P-gp did not changed after being exposed to 0.05 and 0.4 micromol/L ATO for 24, 48 and 72 hours (P>0.05). 3.2 micromol/L ATO could remarkably reduce the expression of P-gp in K562/A02 cells after 48- and 72-hour incubation with ATO (P<0.05). CONCLUSIONS: The down-regulation of P-gp and VEGF after being exposed to ATO probably contributes to the reversion of multidrug resistance in K562/A02 cells. The level of VEGF may be related to the expression rate of P-gp in K562/A02 cells.

[Inhibitory effects of Scutellaria barbatae D. Don on tumor angiogenesis and its mechanism].

BACKGROUND & OBJECTIVE: Various chemically synthetic anti-angiogenesis agents have serious side effects. The traditional Chinese medicine has attracted considerable attention because of its low toxicity. This study was to explore the inhibitory effects of Scutellaria barbatae D. Don, a kind of traditional Chinese medicinal anti-cancer herb, on tumor angiogenesis, and investigate its mechanism. METHODS: Matrigel plug and human umbilical vascular endothelial cells (HUVECs) were used to construct in vivo and in vitro models of angiogenesis to assess the effect of Scutellaria barbatae D. Don on angiogenesis. After cultured with Scutellaria barbatae D. Don, the migration of endothelial cells was examined by Transwell chamber; the expression of vascular endothelial growth factor (VEGF) in HeLa cells was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Scutellaria barbatae D. Don significantly inhibited angiogenesis in Matrigel; the tube formation number was significantly lower in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (5.6+/-1.1 vs. 9.8+/-1.3, P=0.001; 1.0+/-0.7 vs. 13.4+/-1.1, P<0.001). Migrated endothelial cells was significantly fewer in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (19.75+/-2.63 vs. 24.25+/-2.06, P=0.038; 14.00+/-2.58 vs. 26.5+/-4.65, P=0.006). When treated for 24 h and 48 h, the expression of VEGF in HeLa cells was significantly lower in 40% medicated serum group containing Scutellaria barbatae D. Don than in 40% drug-free serum group (138.67+/-9.50 vs. 195.82+/-2.43, P=0.006; 93.84+/-41.11 vs. 193.68+/-18.37, P=0.036). CONCLUSION: Scutellaria barbatae D. Don could efficiently inhibit angiogenesis in tumor tissue which might relate with inhibition of endothelial cell migration and down-regulation of VEGF in tumor cells.