GubenyiliuⅡ inhibits breast tumor growth and metastasis associated with decreased heparanase expression and Akt phosphorylation

作者：ZHANG Yi; ZHANG Gan-lin; SUN Xu; CAO Ke-xin; SHANG Ya-wen; GONG Mu-xin; MA Cong; NAN Nan; LI Jin-ping; YU Ming-wei; YANG Guo-wang; WANG Xiao-min

来源：中国药理学与毒理学杂志, 2016, 30(10): 1076.

OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.

• 单位
  首都医科大学