Anti-tumour combined pharmaceutical composition and application thereof

A composition and anti-tumor technology, applied in the field of biomedicine, can solve the problem of high market price, and achieve the effects of reducing the weight of the spleen, reducing the dosage of administration, and improving the curative effect of patients

Active Publication Date: 2021-02-23
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the market price of trabectedine is as high as 13,000 yuan/mg, an

Method used

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  • Anti-tumour combined pharmaceutical composition and application thereof
  • Anti-tumour combined pharmaceutical composition and application thereof
  • Anti-tumour combined pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] In this embodiment, by measuring the IC50 values ​​of Trabectedin and enterolactone ENL, the administration concentration and synergy index (Combination Index) of the two are determined.

[0049] (1) In this example, human epithelial ovarian cancer cell line A2780 was treated with enterolactone ENL at concentrations of 50, 200, 400, 600, 800, 1000 and 1200 μM / L, and the concentrations were 50, 100, 150 and 200 μM / L. , 250, 300, 400 and 500μM / L enterolactone ENL to treat the human epithelial ovarian cancer cell line ES-2, with concentrations of 1, 2, 3, 4, 5, 6, 8 and 10nM / L. Human epithelial ovarian cancer cell line A2780 was treated with Trabectedin, human epithelial ovarian cancer cell line was treated with Trabectedin at concentrations of 1, 2, 3, 4, 5, 6, 8 and 10 nM / L ES-2.

[0050] Ovarian cancer clear cell carcinoma cell lines ES-2 (McCoy’s 5A medium) and A2780 (DMEM / 1640 medium) were purchased from ATCC.

[0051] According to the mortality rate of ovarian canc...

Embodiment 2

[0062] Since tumor invasion and metastasis are the main factors leading to poor prognosis of cancer, and angiogenesis is an important way for tumor implantation after metastasis, this example divides the experiment into Ctrl group, Trabectedin group, ENL group, and T+E combined drug experimental group, respectively, the combined drug of ENL and Trabectedin inhibited the proliferation, activity, and migration of ovarian cancer cells, promoted cell apoptosis, and inhibited angiogenesis. Tested.

[0063] In this embodiment, the dosage of Trabectedin in the Trabectedin group was 5 nM, the dosage of ENL in the ENL group was 150 μM, and the dosage of Trabectedin in the T+E combination experiment group was 2.5 nM+ENL dosage was 75 μM.

[0064] (1) The inhibitory effect of ENL combined with Trabectedin on the proliferation of ovarian cancer cell lines ES-2 and A2780 cells was tested by CCK-8 cell proliferation assay.

[0065] Experimental method: Cells are normally passaged, and the ...

Embodiment 3

[0089] In this embodiment, after determining the concentration of ENL and Trabectedin, the experiment is divided into Ctrl group, Trabectedin group, ENL group and T+E combined drug experiment group, wherein the Trabectedin dosage of Trabectedin group is 5nM, ENL group The dosage of ENL in T+E combined drug group was 2.5nM+ENL dosage was 75μM.

[0090] In this example, THBS-1 was used as the core protein for experiments based on gene sequencing and KEGG database access. The effects of different treatment factors: Ctrl, ENL, Trabectedin, and T+E on the expression levels of THBS1 and related pathway gene proteins and mRNA in ovarian cancer cells after 24 hours were tested.

[0091] (1) The effect of ENL combined with Trabectedin on the mRNA expression of THBS1 and related pathway genes (THBS1, CD36, TIMP3, VEGFR2, MMP9, CD47) in ovarian cancer cell line ES-2 was tested by Real-Time PCR experiment.

[0092] In order to observe the effect of overexpression of THBS-1 on ovarian can...

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Abstract

The invention relates to an anti-tumour combined pharmaceutical composition and application thereof, and belongs to the field of biological medicines. In order to further improve the cancer treatmenteffect and reduce the drug cost of applying trabectedin at the same time, the invention provides an anti-tumour combined pharmaceutical composition, which comprises an effective amount of enterolactone or a plant lignan precursor capable of being converted into enterolactone in a body, and further comprises an effective amount of trabectedin. According to the invention, experiments prove that combined application of trabectedin and enterolactone can inhibit proliferation, activity, metastasis, invasion and angiogenesis of ovarian cancer and promote tumour cell apoptosis; and, when the two drugs are combined for use, the inhibition effect on the ovarian cancer is stronger than that of a single drug after the dosage of the two drugs is halved. According to the invention, the administration amount of trabectedin is reduced by using the enterolactone with lower cost; the economic burden of a patient is reduced; and the enterolactone can also reduce the side effect of trabectedin. The combined pharmaceutical composition disclosed by the invention can improve the anti-tumour curative effect and promote clinical popularization of trabectedin.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to an anti-tumor combined pharmaceutical composition and its application. Background technique [0002] Thrombospondin-1 (thrombospondins-1, THBS-1) is the first discovered natural angiogenesis inhibitor, which includes six active domains. The active domain of THBS-1, the three typeⅠrepeats (3TSR), can bind to CD36, activate P38MAPK and caspase-3, inhibit the migration of endothelial cells and promote their apoptosis, thereby inhibiting angiogenesis. This way of inhibiting angiogenesis plays a very important role in the suppression of cancer. [0003] CD47 is another receptor that binds to THBS-1 and can bind to the C-terminus of THBS-1. The combination of CD47 and THBS-1 can enhance the drug resistance of melanoma and promote the invasion of glioma, and blocking their combination can protect normal tissues from radiation damage. [0004] Vascular endothelial growth factor-...

Claims

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Application Information

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IPC IPC(8): A61K31/4995A61P35/00A61P35/04A61K31/05A61K31/34A61K31/351A61K31/36
CPCA61K31/4995A61K31/05A61K31/34A61K31/351A61K31/36A61P35/00A61P35/04A61K2300/00
Inventor 刘慧迪刘树林曾峥林彩姬王鹏飞林益如
Owner HARBIN MEDICAL UNIVERSITY
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