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Study on Antifibrosis and Antitumor of Breviscapine

Author: WuXianChuang
Tutor: DuGangJun
School: Henan University
Course: Pharmacology
Keywords: Breviscapine Antitumor Antifibrotic TGF-β1 Antimetastatic
CLC: R285
Type: Master's thesis
Year: 2010
Downloads: 105
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Abstract

The flavonoids breviscapine has strong free radical scavenging, antioxidant, antimicrobial, antithrombotic variety of pharmacological effects, the research group found its good inhibition of TGF-β1 This role is to prevent tissue fibrosis and anti-tumor is the focus of our exploration. The purpose of this study was to explore the breviscapine antifibrotic and anti-tumor effect and its possible mechanism of action. Model and BLM lung fibrosis model in mice using the MTT assay Breviscapine vitro rat hepatic stellate cell HSC, T lymphocytes and K562 proliferation of this article; mouse CC14 liver damage (fibrosis), evaluation Dengzhanhua factors after the administration of the protective effect of liver fibrosis and pulmonary fibrosis, and detection of tissue antioxidant enzyme activities (such as peroxidase, catalase and superoxide dismutase), TGF-β1, TNF-α and MDA content; Lewis lung carcinoma subcutaneous transplantation tumor models of lung metastases model the evaluation Breviscapine body alone and inhibition of tumor combined with radiotherapy or chemotherapy, and to evaluate the role of combined radiotherapy and chemotherapy Reducing Toxicity; 4T1 breast carcinoma transplanted subcutaneously in tumor models, the evaluation Breviscapine prevention of recurrence and metastasis of tumor resection. The in vitro cell culture: breviscapine 50μmol / L of cultured mouse spleen lymphocytes proliferation significant role in promoting the best concentration to 10 μmol / L, no significant change on cultured HSC cell morphology, lactate dehydrogenase release and cell proliferation were not significantly affected, but inhibit the proliferation of TGF-β1-induced HSC cells, IC50 22.04μmol / L (95% CI 13.94-34.19μmol / L). Breviscapine 100μg/ml K562 cell growth inhibition, breviscapine in 10-100μg/ml concentration range had no significant effect on lymphocyte growth, but can enhance the resistance of mouse lymphocytes doxorubicin promote adriamycin induced K562 cell growth inhibition. ELISA apoptosis detection and flow cytometry apoptosis detection breviscapine 10 or 30μg/ml significantly promote apoptosis of K562 cells induced by doxorubicin. Rat of CC14 liver fibrosis model in rat serum ALT and AST were 571.35U / L, and 514.52U / L (normal 56.73 and 139.27U / L), respectively 10-fold and 3.69-fold normal rats ; of breviscapine ig100mg/kg treatment serum ALT and AST 218.22U / L and 247.81U / L, reduced by 38.19% and 48.16% respectively as compared with the untreated group. Breviscapine (ig100mg/kg) treatment of rat liver hydroxyproline feeding acid, collagen, MDA and TGF-β1 increased significantly reduced role, and POD, CAT and total SOD, Cu-ZnSOD activity reduced were significantly elevated role; same model of pulmonary fibrosis in mice BLM breviscapine (ig100mg/kg) of BLM-induced mouse lungs POD, CAT, total SOD, Cu-ZnSOD activity reduction. rise significantly reduce elevated levels of TGF-β in serum hydroxyl feeding acid, collagen, MDA and lung tissue. Of subcutaneously transplanted tumor and lung metastasis of Lewis lung tumor model in breviscapine be used alone or with good anti-tumor and tumor metastasis inhibition; radiotherapy or chemotherapy use not only able to produce synergistic anti-tumor effect, but also be able to inhibit or even eliminate radiotherapy or chemotherapy arising from damage to the hematopoietic system; either prolong the survival time of tumor-bearing mice, without affecting the state of the tumor-bearing mice and weight. 4T1 breast subcutaneous xenograft model after surgical resection of tumor recurrence and metastasis rate of the control group 50% and 70%, the rate of tumor recurrence and metastasis rate of breviscapine (ig200mg/kg) treated mice surgical resection 20% and 20%. Mechanism: breviscapine vitro mouse spleen cell proliferation induced by ConA enhanced role in the inhibition of TGF-β1 and IL-4, the promotion of IFN-γ and IL-2 secretion; breviscapine promote doxorubicin-induced K562 cell growth inhibition, release of cytochrome C, caspase-8 and caspase-3 activation, raised its p53/bcl-2 expression ratio and increased apoptosis. In summary, Dengzhanhua known as the definitive anti-fibrosis and anti-tumor effect, good synergy with radiation and chemotherapy, and can inhibit the side effects of radiotherapy and chemotherapy, the mechanism is the inhibition of TGF-β1 to lifting the tumor immune escape and activation of tumor cell apoptosis pathway.

Study on Antifibrosis and Antitumor of Breviscapine

Abstract

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