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Application of Tagalsin C and its homologous compound in preparing anti-tumor medicine

A technology of anti-tumor drugs and homologues, applied in the field of drugs, can solve problems such as drug resistance and cancer recurrence, and achieve the effect of broad application prospects

Inactive Publication Date: 2007-11-28
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Not only that, tumor cells can develop drug resistance during treatment, leading to cancer recurrence

Method used

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  • Application of Tagalsin C and its homologous compound in preparing anti-tumor medicine
  • Application of Tagalsin C and its homologous compound in preparing anti-tumor medicine
  • Application of Tagalsin C and its homologous compound in preparing anti-tumor medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1, MTT method to detect Tagalsin C and its homologues inhibiting the growth of IM9, IM9 / Bcl-2 and HL-60 cells

[0024] Human myeloma IM9 cells, human myeloma IM9 cells with high expression of Bcl-2 (stable expression cell line IM9 / BcL-2 transfected with human Bcl-2 cDNA), and human leukemia cells HL-60 were mixed at 10 per well. 5 Cells, 100μl / well spread in a 96-well culture plate, add Tagalsin C and its homologues to make three duplicate holes for each compound, at 37°C, 5% CO 2 Incubate in an incubator for 24 hours, add MTT reagent (product of Sigma Company) and mix well, continue to incubate for 3 to 5 hours, and analyze the growth inhibition of different concentrations of drugs on cells by an ELISA plate reader at a wavelength of 570nm.

[0025] The relationship between the growth of tumor cells and the concentration of Tagalsin C is shown in Figure 1, indicating that Tagalsin C has cell membrane permeability and can effectively inhibit the growth of myelom...

Embodiment 2

[0028] Example 2, Tagalsin C and its homologues kill human myeloma cells and other tumor cells with high expression of Bcl-2

[0029] Then we studied whether Tagalsin C and its homologues Tagalsin A, B, D, E, F, G could induce the apoptosis of human myeloma cells and other tumor cells with high expression of Bcl-2. We applied flow cytometry, which is commonly used at home and abroad, combined with FITC-AnnexinV staining, an indicator of apoptosis, to quantitatively detect the apoptosis induced by Tagalsin C and its homologues. Inoculate different types of tumor cells in 24-well plates, then add different concentrations of Tagalsin C and its homologues Tagalsin A, B, D, E, F, G for 24 hours, wash twice with PBS, add FITC-labeled AnnexinV (The kit is provided by Beijing Baosai Biotechnology Co., Ltd.), and the killing effect of the drug on tumor cells is detected by flow cytometry (FACSCalibur, a product of BD Company of the United States).

[0030] Table 1 shows the experiment...

Embodiment 3

[0039] Example 3, Experiment of Tagalsin C Inducing Tumor Cell Nuclear DNA Fragmentation

[0040] Various tumor cells that were normally cultured and treated with Tagalsin C for 24 hours were washed twice with PBS, incubated with PBS containing 0.2% Tween20 at 37°C for 15 minutes, and then specifically mixed with DNA at a final concentration of 0.25 μg / ml (prepared in PBS). The permanent dye DAPI (product of Sigma Company) was reacted at room temperature in the dark for 30 minutes, and the changes of DAPI-stained nuclei during apoptosis were observed under an Olympus fluorescence microscope.

[0041] As shown in Figure 5A, the changes of DAPI-stained nuclei in human lung cancer cell A549 and human cervical cancer epithelial HeLa cells during the apoptosis process and in Figure 5B are the changes of DAPI-stained nuclei in human liver cancer cells HePG2, human macrophage lymphocytes The changes in the apoptosis process of tumor cell U937, human prostate cancer cell PC-3 and huma...

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Abstract

The present invention relates to the application of the metabolite Tagalsin C of marine life and its homologs Tagalsins A, B, D, E, F and G in preparing medicine for treating tumor. The series of compounds has high membrane permeability and broad spectrum antitumor activity of killing human promyelocytic acute leukemia cell HL-60, human myeloma cell IM9, human acute T-cell leukemia cell Jurkat, human macrophage lymphoma cell U937, human lung cancer cell A549, etc, and no obvious injury on health human nephridium cell 293aa human liver diploid cell L02. The series of compounds may be used in preparing medicine for treating tumor, medicine with high clinical Bcl-2 expression and conventional chemotherapy resistance, and medicine for treating cancer recurrence.

Description

technical field [0001] The invention belongs to the field of medicines, in particular to the application of a marine biological metabolite Tagalsin C and its homologues Tagalsins A, B, D, E, F, G in the preparation of antitumor drugs. Background technique [0002] At present, the main treatment method for clinical cancer is chemotherapeutics, that is, the application of large doses of DNA damaging agents. This method has serious side effects, because chemotherapy agents destroy normal cells in large quantities while killing cancer cells. Not only that, tumor cells can develop drug resistance during treatment, leading to cancer recurrence. Therefore, searching for drugs that can selectively kill cancer cells, especially those tumor cells that are resistant to conventional chemotherapy drugs, has become a hot spot in drug development. [0003] There are many reasons for cancer drug resistance. The latest research shows that the drug resistance of cancer is related to the ab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/336A61K31/122C07C13/60C07D203/26A61P35/00
Inventor 林文翰陈英玉顾佳马大龙张婷
Owner PEKING UNIV
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