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Triptolide inhibits cell proliferation by downregulating phosphorylation of
estrogen reporters in 4T1 tumor-bearing mice
PAN Guo-feng1, GAO Jian-li2, ZHANG Qi3, LV Gui-yuan2*, CHEN Su-hong3*
(1. Traditional Chinese Medicine Department, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing , China;
2. Institute of Material Medica, Zhejiang Chinese Medical University, Hangzhou , China;
3. Institute of Chinese Medicine, Wenzhou Medical University, Wenzhou , China)
[Abstract] In order to investigate the anti-proliferative effects of triptolide(TP) on 4T1 mice breast cancer cell line in vitro and in mouse model, as well as the possible mechanisms, we detected the effect of TP on cell proliferation by MTT assay or Crystal Violet Staining in our research. Flowcytometry combined with FITC-Annexin V/PI staining were used for detecting TP induced 4T1 cell apoptosis. The protein expression of ERα, p-ERα, ERβ, p-ERβ, ERK, p-ERK, p38, p-p38, SAPK/JNK, and p-SAPK/JNK was tested by western blotting. We also compare TP with chemotherapy drug doxorubicin in 4T1 tumor bearing BLAB/c mice model, the Xenogen bioluminescence imaging, H&E, and IHC result indicated that TP exhibits an anticancer proliferation activity. As a result, TP in 100,10,1,0.1 μmol·L-1, all inhibited the proliferation of 4T1 cells by MTT assay and Crystal Violet Staining. TP which concentrations is 10,1,0.1 μmol·L-1could induce the apoptosis of 4T1 cells and reduce the cell proliferation. TP in 200 μg·kg-1 could inhibit the tumor growth in vivo. The anticancer proliferation of TP was involved in its effect on reducing expression of ERα, p-ERα, ERβ, and p-ERβ, but nothing to do with the activation of MAPK signaling pathway.
[Key words] triptolide; 4T1 mice breast cancer; tumor cell proliferation; estrogen receptor;bioluminescence imaging
doi:10.4268/cjcmm