OBJECTIVE: Triple-negative breast cancer (TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu (TBM), the rhizome of Bolbostemma paniculatum (Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu (ETBM) on TNBC orthotopic mouse models and cell lines. METHODS: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis applied to explore the pathways influenced by ETBM. Moreover, quantitative real-time polymerase chain reactions (qRT-PCR) and Western blot were delivered to confirm the gene expression changes. RESULTS: ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1 (ITGβ1), integrin β8 (ITGβ8) and Rho GTPase activating protein 5 (ARHGAP5), which disabled the focal adhesion pathway and caused change in cell morphology. CONCLUSIONS: This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.
OBJECTIVE: Triple-negative breast cancer (TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu (TBM), the rhizome of Bolbostemma paniculatum (Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu (ETBM) on TNBC orthotopic mouse models and cell lines. METHODS: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis applied to explore the pathways influenced by ETBM. Moreover, quantitative real-time polymerase chain reactions (qRT-PCR) and Western blot were delivered to confirm the gene expression changes. RESULTS: ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1 (ITGβ1), integrin β8 (ITGβ8) and Rho GTPase activating protein 5 (ARHGAP5), which disabled the focal adhesion pathway and caused change in cell morphology. CONCLUSIONS: This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.
Entities:
Keywords:
Rho GTPase activating protein 5; Traditional Chinese Medicine (TCM); Tubeimu; integrins; orthotopic mouse models; triple negative breast cancer (TNBC)
Authors: Bryan P Schneider; Eric P Winer; William D Foulkes; Judy Garber; Charles M Perou; Andrea Richardson; George W Sledge; Lisa A Carey Journal: Clin Cancer Res Date: 2008-12-15 Impact factor: 12.531