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MechanismofactionofcurcumincombinedwithmitomycinCinreducingtoxicityandenhancingefficacyinthetreatmentofbreastcancer

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登记号:G20251429

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学科分类:

关键词: Curcumin Breast Cancer Mitomycin C

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成果名称: MechanismofactionofcurcumincombinedwithmitomycinCinreducingtoxicityandenhancingefficacyinthetreatmentofbreastcancer
成果登记号: G20251429 学科分类:
绿色分类: 项目关键词: Curcumin   Breast Cancer   Mitomycin C    
推荐单位:

Shanghai University of Traditional Chinese Medicine

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国家/地区: Shanghai 知识产权: Other
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This project falls within the research field of integrated traditional Chinese and Western medicine and pharmacology of traditional Chinese medicine. Mitomycin C (MMC) is a commonly used and relatively inexpensive broad-spectrum antitumor drug, but its significant and persistent adverse reactions such as bone marrow suppression, nephrotoxicity, and gastrointestinal reactions have limited its clinical application. Curcumin is an edible natural yellow pigment obtained by extracting and refining from the traditional Chinese medicinal material turmeric. It has a wide range of pharmacological effects including antiviral and anti-inflammatory properties, reducing cholesterol, inhibiting platelet aggregation, increasing fibrinolytic activity, antioxidation, anti-mutation, anticarcinogenicity, and anticancer promotion activities, and it is also very safe. Literature reports have shown that curcumin can improve the toxic side effects caused by various drugs. This project uses breast cancer cell models and transplanted tumor nude mouse models to conduct in vivo and in vitro experiments, Explain the effects and mechanisms of action of the combination of curcumin and MMC, achieving a series of innovative results. Through in vivo human breast cancer xenograft nude mouse model experiments, it was found that curcumin enhanced the inhibition of tumor growth by MMC, which is related to the combined use inducing apoptosis of tumor cells; at the same time, it was discovered that curcumin improved the renal function damage and bone marrow growth inhibition caused by MMC, and the mechanism by which the combined use alleviated the toxic side effects of MMC is related to its reduction in GRP58-mediated DNA crosslinking and its decrease in the accumulation of MMC in the kidneys. Through in vitro culture experiments with human breast cancer cell lines, it was found that curcumin combined with MMC inhibited the proliferation of breast cancer cells, which is related to the combined use inducing apoptosis and causing cell cycle arrest. The combination of drugs has blocked the 'p38 MAPK-GRP58-p53' pathway. This project is characterized by the comprehensive application of breast cancer in vitro and in vivo models, traditional Chinese medicine (TCM) and Western medicine combination screening and computational methods, as well as transcriptomics and molecular/cellular biology techniques, to conduct experimental research on the treatment of breast cancer with TCM and Western medicine combinations. It elucidates the effects, safety, and mechanisms of TCM and Western medicine combination application in the treatment of breast cancer, and for the first time confirms that curcumin combined with mitomycin C has a synergistic effect on reducing toxicity in the treatment of breast cancer, which is related to the inhibition of the 'p38 MAPK-GRP58-p53' pathway. Through the research of this project, a total of 14 related academic papers have been published, including 6 that were indexed by SCI, and one national invention patent application has been made based on the research results. Participation in domestic and international relevant academic conferences has also been undertaken 6 times. Train 2 young teachers, train 2 graduate students, and train 1 undergraduate intern. The project technology has been promoted and applied in multiple hospitals, and the research findings have been widely published and reported on various domestic websites. This project provides a scientific experimental basis for the prevention and treatment of breast cancer with the combination of traditional Chinese medicine and Western medicine, expands ideas for further improving the efficacy and safety of treating breast cancer in the future, and provides theoretical basis and reference for basic research.
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