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, i...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(q RT-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.展开更多
OBJECTIVE: To establish a "life system tuning model", which will provide theoretical and methodological basis to solve various medical problems such as the diagnosis and treatment of complex diseases. METHOD...OBJECTIVE: To establish a "life system tuning model", which will provide theoretical and methodological basis to solve various medical problems such as the diagnosis and treatment of complex diseases. METHODS: First of all, by using the approaches of systems biology, bioinformatics, and systems engineering, we set DNA as the center of this model, which severs as a bridge linking the characteristics of a disease with the pharmacological properties of the treating medicine. Secondly, the model shows how to employ molecular markers to dissect the pharmacological property of the drug, and the relation between the pharmacological property of the drug and its clinical administration.Also demonstrates how to discover therapeutic targets and to develop targeted medicine based on the biochemical features of the patients, which reflect their physiological and pathological body environment. Finally, the model uses systems biology data to determine molecular mechanisms underlying the disease and subtype, then employ precision methods to adjust the function of some master molecules. RESULTS: Based on the genetic information, this model integrates the diagnostic information from Western medicine and the disease pattern classification of TCM that is generated from the four diagnostic methods of "inspection, auscultation and olfaction, inquiry and pulse-taking and palpation". This model also integrates various disease intervention approaches including physical methods, chemical methods, and psychological methods. CONCLUSIONS: The establishment of this model provides a basis for personalized treatment of disease using various methods, for the protection and exploration of various natural resources used in TCM, and for the standardization of TCM.展开更多
基金supported by National Natural Science Foundation of China Grant (No. 81303129)Beijing University of Chinese Medicine Grant (Project ID: 2016-jxs-548)
文摘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(q RT-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.
文摘OBJECTIVE: To establish a "life system tuning model", which will provide theoretical and methodological basis to solve various medical problems such as the diagnosis and treatment of complex diseases. METHODS: First of all, by using the approaches of systems biology, bioinformatics, and systems engineering, we set DNA as the center of this model, which severs as a bridge linking the characteristics of a disease with the pharmacological properties of the treating medicine. Secondly, the model shows how to employ molecular markers to dissect the pharmacological property of the drug, and the relation between the pharmacological property of the drug and its clinical administration.Also demonstrates how to discover therapeutic targets and to develop targeted medicine based on the biochemical features of the patients, which reflect their physiological and pathological body environment. Finally, the model uses systems biology data to determine molecular mechanisms underlying the disease and subtype, then employ precision methods to adjust the function of some master molecules. RESULTS: Based on the genetic information, this model integrates the diagnostic information from Western medicine and the disease pattern classification of TCM that is generated from the four diagnostic methods of "inspection, auscultation and olfaction, inquiry and pulse-taking and palpation". This model also integrates various disease intervention approaches including physical methods, chemical methods, and psychological methods. CONCLUSIONS: The establishment of this model provides a basis for personalized treatment of disease using various methods, for the protection and exploration of various natural resources used in TCM, and for the standardization of TCM.