Application of genipin in preparation of medicine for inhibiting breast cancer angiogenesis

Abstract

The invention relates to a medicine for inhibiting breast cancer angiogenesis, and discloses an application of genipin in preparation of the medicine for inhibiting breast cancer angiogenesis. Research results of the invention show that the genipin can directly inhibit expression of HIF-1alpha so as to interfere hypoxia-related pathways and prevent hypoxia-related transcription factors from playing a role. In addition, the genipin can also reduce the expression of HSPG2, so that the accumulation of extracellular matrix components is reduced, and cell proliferation, migration and angiogenesis damage are finally caused, and therefore, the genipin can be used for preparing the medicine for inhibiting breast cancer angiogenesis.

Description

Technical Field

[0001] The present invention relates to a drug for inhibiting breast cancer angiogenesis, and particularly to the application of genipin in the preparation of a drug for inhibiting breast cancer angiogenesis. Background Art

[0002] Breast cancer (BRCA) is one of the most common cancers in women, which is highly heterogeneous and exhibits different morphological features, biological behaviors, and treatment responses. According to molecular markers, BC can be divided into three main molecular subtypes, which require different treatment methods: hormone receptor-positive / ERBB2 (formerly HER2)-negative, ERBB2-positive, and triple-negative BC (TNBC). Although there are targeted therapies for each subtype, the decline in efficacy remains a challenge, highlighting the need for new treatment strategies.

[0003] Angiogenesis refers to the formation of new blood vessels from existing vascular structures, involving the degradation of the basement membrane and the activation, migration, and proliferation of endothelial cells. This process is controlled by a variety of angiogenesis-promoting or -inhibiting factors, including vascular endothelial growth factor, growth factors, TGF-β, TNF-α, integrins, adhesion molecules, and matrix-degrading enzymes. Tumor angiogenesis supports the rapid proliferation of cancer cells by providing oxygen and nutrients, driven by an imbalance between pro-angiogenic and anti-angiogenic factors. However, the newly formed tumor blood vessels are often disordered, showing structural and functional abnormalities, leading to hypoxia, reduced immune cell infiltration, and increased metastatic potential. Therefore, the tumor microenvironment (TME) is characterized by an acidic, hyperbaric, and hypoxic state, which exacerbates angiogenesis. Given the crucial role of angiogenesis in tumor growth, anti-angiogenic therapy is considered a strategy to inhibit tumor progression, which can starve the tumor of nutrients while improving perfusion, thereby enhancing the efficacy of chemotherapy.

[0004] Angiogenesis is indispensable in both physiological and pathological processes. Among them, hypoxia-inducible factor-1α (HIF-1α), as a transcription factor, is closely involved through its response to hypoxic conditions, which are characteristic of most solid tumors. Hypoxia-driven pathways affect angiogenesis, growth factor signal transduction, glycolysis, genetic instability, invasion, metastasis, apoptosis, pH control, and immortalization. In BC, hypoxia stimulates angiogenesis through the HIF-1A / VEGF axis, which is crucial for blood vessel development. The expression of HIF-1α is associated with poor prognosis, enhanced metastatic potential, and increased drug resistance in BC.

[0005] HSPG2, also known as heparan sulfate proteoglycan, is a major extracellular matrix component involved in basement membrane stability. This protein contains heparan sulfate side chains that can bind various pro-angiogenic factors, mainly FGF and VEGF, promoting their storage and transport, which is crucial for angiogenic signaling. High expression of HSPG2 in BC is associated with poor prognosis, especially in TNBC. In addition, HSPG2 can also regulate the adhesion and migration of endothelial cells and promote tumor angiogenesis through the VEGF / VEGFR axis.

[0006] Genipin is derived from the shrub Gardenia jasminoides Ellis of the Rubiaceae family and has the effect of inhibiting angiogenesis. In the chicken embryo chorioallantoic membrane assay, it can inhibit the vascular development of chicken embryos in a concentration-dependent manner. However, its role in tumor angiogenesis related to BC has not been explored. Summary of the Invention

[0007] The present invention provides an application of genipin in the preparation of a drug for inhibiting breast cancer angiogenesis in view of the problem in the prior art regarding whether genipin plays a role in tumor angiogenesis related to BC.

[0008] To solve the above technical problems, the present invention is solved by the following technical solutions: The present invention provides two applications of genipin: an application in the preparation of a drug for inhibiting the proliferation and / or migration of breast cancer cells, specifically, genipin regulates the proliferation and / or migration of breast cancer cells by targeting HSPG2.

[0009] It also provides an application of genipin in the preparation of a drug for inhibiting breast cancer angiogenesis, specifically, genipin inhibits breast cancer angiogenesis by regulating the expression of HSPG2 through the genipin pathway, where genipin inhibits the / HSPG2 signaling axis to regulate the / HSPG2 pathway to inhibit breast cancer angiogenesis.

[0010] The present invention treated breast cancer cells, especially MDA-MB-231 and BT-549, with different doses of genipin. The results showed that genipin dose-dependently reduced cell viability, that is, a certain concentration of genipin could significantly inhibit the proliferation, migration and invasion of MDA-MB-231 and BT-549 cells, showing a dose-dependence In addition, transcriptome sequencing was performed on MDA-MB-231 cells treated with genipin. The analysis showed that HSPG2 plays a key role in vascular development and angiogenesis, indicating that it plays a potential regulatory role in the genipin-mediated effect.

[0011] Western blot analysis of drug-treated MDA-MB-231 and BT-549 cells showed that genipin dose-dependently reduced the level.

[0012] BC cells were treated with genipin and the known stabilizer dimethyloxalylglycine (DMOG). The results showed that DMOG treatment could restore the level inhibited by genipin.

[0013] In summary, these findings indicate that genipin regulates the expression of HSPG2 through the pathway, thereby regulating angiogenesis in BC cells. Genipin targets HSPG2 and regulates the migration and angiogenesis of MDA-MB-231 and BT-549 cells. Brief Description of the Drawings

[0014] Figure 1 is the structural formula of genipin of the present invention. Detailed Description of the Invention

[0015] The present invention will be further described in detail below with reference to the drawings and embodiments.

[0016] Example 1 The present invention provides the use of genipin in the preparation of a drug for inhibiting the proliferation and / or migration of breast cancer cells. Specifically, genipin regulates the proliferation and / or migration of breast cancer cells by targeting HSPG2.

[0017] The present invention also provides the use of genipin in the preparation of a drug for inhibiting breast cancer angiogenesis. Specifically, genipin inhibits breast cancer angiogenesis by regulating the expression of HSPG2 through the genipin through the pathway, wherein the structural formula of genipin is as shown in Figure 1 , and it inhibits breast cancer angiogenesis by inhibiting the / HSPG2 signaling axis to regulate the / HSPG2 pathway.

[0018] In the present invention, breast cancer cells, especially represented by MDA-MB-231 and BT-549, were treated with different doses of genipin. The results showed that genipin dose-dependently reduced cell viability, that is, a certain concentration of genipin could significantly inhibit the proliferation, migration and invasion of MDA-MB-231 and BT-549 cells, showing a dose-dependent manner In addition, transcriptome sequencing was performed on genipin-treated MDA-MB-231 cells. The analysis showed that HSPG2 plays a key role in blood vessel development and angiogenesis, indicating its potential regulatory role in genipin-mediated effects.

[0019] Western blot analysis of drug-treated MDA-MB-231 and BT-549 cells showed that genipin dose-dependently reduced levels.

[0020] BC cells were treated with genipin and the known stabilizer dimethyloxalylglycine (DMOG). The results showed that DMOG treatment could restore the levels inhibited by genipin.

[0021] In summary, these findings indicate that genipin regulates the expression of HSPG2 through the pathway, thereby regulating angiogenesis in BC cells. Genipin targets HSPG2 and regulates the migration and angiogenesis of MDA-MB-231 and BT-549 cells.

[0022] It is easy to understand that those skilled in the art can combine, split, recombine, etc. the embodiments of the present application based on one or several embodiments provided by the present application to obtain other embodiments, and these embodiments do not exceed the protection scope of the present application.

[0023] In summary, the above are only the preferred embodiments of the present invention, and all equivalent changes and modifications made according to the scope of the patent application of the present invention shall fall within the scope covered by the patent of the present invention.

Claims

1. Use of genipin in the preparation of a drug for inhibiting the proliferation and / or migration of breast cancer cells.

2. The application according to claim 1, wherein: The genipin regulates the proliferation and / or migration of breast cancer cells by targeting HSPG2.

3. Use of genipin in the preparation of a drug for inhibiting breast cancer angiogenesis.

4. The application according to claim 1, wherein: Genipin regulates the expression of HSPG2 through the pathway to inhibit breast cancer angiogenesis.

5. The application according to claim 4, wherein: The genipin inhibits / HSPG2 signaling axis to regulate / HSPG2 pathway to inhibit breast cancer angiogenesis.

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