ABSTRACT
Aim To investigate the effect of baicalein on the reversal of multidrug resistance ( MDR) media-ted by breast cancer resistance protein ( BCRP) in hu-man breast cancer MCF-7/MX cells, and explore the possible mechanisms. Methods MTT assay was per-formed to determine the cytotoxicity of baicalein and susceptibility of chemotherapeutic drugs. The protein expression levels of BCRP, p-p38 MAPK and NF-κB p65 were determined by Western blot. Results MCF-7/MX cells were not only resistant to MX but cross-re-sistant to 5-FU and DDP, and the resistance index was 70. 45, 6. 68 and 21. 47, respectively. 2. 5, 5μmol· L-1 of baicalein could increase the sensitivity to above chemotherapeutic agents and decrease the expression levels of BCRP, p-p38 MAPK and NF-κB p65 in MCF-7/MX cells. Conclusion Baicalein can effec-tively reverse MDR of MCF-7/MX by down-regulating BCRP expression through p38/MAPK and NF-κB path-ways.
ABSTRACT
AIM:To investigate the effects of baicalein on pulmonary arterial hypertension(PAH)induced by monocrotaline(MCT)in rats,and its molecular mechanism was further explored.METHODS: Male SD rats(n=28) were randomly divided into 4 groups: control group, MCT group, MCT+baicalein 50 mg/kg group and MCT +baicalein 100 mg/kg group.The PAH model was established by subcutaneous injection of MCT.After 2 weeks of modeling,the rats in baicalein treatment groups were gavaged baicalein 50 and 100 mg· kg -1· d-1for 14 d,the rats in control group were administered with saline.After 4 weeks of modeling,right ventricular systolic pressure(RVSP),right ventricular hypertro-phy index(RVHI)and right ventricular mass index(RVMI)were detected.Masson staining was used to detect the degree of lung fibrosis.The pathomorphological changes of the pulmonary vessels were observed by HE staining.Western blot was used to detect the expression of α-smooth muscle actin(α-SMA)in the lung tissue and the phosphorylation p 38,ERK and JNK in the artery.RESULTS:Compared with the control group,RVSP, RVHI and RVMI increased significantly in the MCT group(P<0.01).Pulmonary fibrosis and the thickening of pulmonary artery wall were observed.α-SMA was up-regulated and p38,ERK and JNK was activated significantly(P<0.01).Compared with the MCT group,baicalein(50 and 100 mg/kg)significantly decreased the RVSP,RVHI and RVMI(P<0.01).Lung fibrosis was reduced and the vas-cular wall thickening was decreased in baicalein-treated groups.Baicalein(50 and 100 mg/kg)inhibited the phosphoryla-tion of p38,ERK and JNK compared with the MCT group(P<0.01).CONCLUSION:Baicalein ameliorates MCT-in-duced PAH by the inhibition of pulmonary artery wall thickening at least partially via MAPK signaling pathway.