CN113244228A - Application of GL-V9 in preparation of anti-glioma drug - Google Patents
Application of GL-V9 in preparation of anti-glioma drug Download PDFInfo
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- CN113244228A CN113244228A CN202011522216.6A CN202011522216A CN113244228A CN 113244228 A CN113244228 A CN 113244228A CN 202011522216 A CN202011522216 A CN 202011522216A CN 113244228 A CN113244228 A CN 113244228A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention provides application of a flavonoid derivative GL-V9 in preparation of a brain glioma-resisting medicine. Further research shows that GL-V9 can obviously inhibit the growth activity of glioma cells, can obviously promote early and late apoptosis of glioma U87 cells, and has an application prospect in developing anti-glioma drugs.
Description
Technical Field
The invention belongs to the field of antitumor drugs, and particularly relates to an application of a compound GL-V9 in preparation of a brain glioma-resistant drug.
Background
Brain gliomas are the most common primary craniocerebral tumors arising from brain and spinal glioblastomas canceration. The annual incidence is about 3-8 people per 10 million people. Gliomas are caused by the interplay of innate genetic high risk factors and environmental carcinogens. Some known genetic diseases, such as neurofibromatosis (type I) and tuberculous sclerosis, are genetic predisposing factors for brain gliomas.
The World Health Organization (WHO) divides brain glioma into four grades, wherein more than half of the brain glioma is the polymorphic glial cell (GBM) with the highest degree of malignancy, and the GBM has local heterogeneity, high invasiveness and high growth speed, so that the surgery is difficult to completely remove, the brain glioma is easy to relapse, and the brain glioma is easy to generate drug resistance. And most of the drugs can not directly reach the tumor part due to the existence of the blood brain barrier, and at present, the structure of the blood brain barrier is not very clear, and particularly, the transfer mechanism is not clear, so that not all the drugs can pass through the blood brain barrier, and further, the treatment difficulty and the prognosis of the malignant glioma are further caused.
Temozolomide is an alkylating agent, is a first-line chemotherapeutic drug for treating brain glioma which is commonly used clinically at present, has good central nervous system permeability and biological availability when being taken orally, but has poor clinical effect according to the evidence of the current circulating medicine, the 5-year survival rate of newly-diagnosed GBM is only 9.8% by adopting the standard temozolomide-assisted chemotherapy, drug resistance and systemic toxic and side effects are easy to generate, and most patients still have difficulty in avoiding tumor recurrence. Therefore, the natural medicinal materials which are beneficial to the treatment of the brain glioma can be found to have important significance.
Disclosure of Invention
In order to improve the technical problem, the invention provides application of a flavonoid derivative GL-V9 in preparation of a brain glioma resistant medicament.
According to an embodiment of the present invention, the brain glioma may be U87 cells;
according to an embodiment of the present invention, the GL-V9 can inhibit the growth activity of brain glioma U87 cell;
according to an embodiment of the present invention, the GL-V9 can promote early and/or late apoptosis of brain glioma U87 cells.
Advantageous effects
The research of the invention finds that the flavonoid derivative GL-V9 can obviously inhibit the growth activity of brain glioma cells. Further, cell apoptosis detection experiments show that GL-V9 can remarkably promote early and late apoptosis of brain glioma U87 cells, and the GL-V9 can be used for treating brain glioma and has an application prospect in developing anti-brain glioma drugs.
Drawings
FIG. 1 is a line graph showing the inhibition rate of GL-V9 on glioma cell lines at different concentrations.
FIG. 2 is a graph of apoptosis test of brain glioma cells with different concentrations of GL-V9.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
Experimental Material
1.1 reagents
(1)GL-V9(C24H27O5N, molecular weight: 409.47) was supplied by university of Chinese pharmacy in the form of pale yellow powder with a purity of greater than 99%, and the drug powder was prepared as a 0.02M stock solution with dimethyl sulfoxide (DMSO) prior to use and stored at-20 ℃. Immediately before use, M containing 10% fetal bovine serumEM culture solution is prepared to the required concentration.
(2) Cell culture reagent
Culture solution: MEM medium, purchased from GIBCO, USA. Before use, 100U/ml penicillin and 100U/ml streptomycin are added.
② fetal bovine serum: product of GIBCO, usa. Inactivating in 56 deg.C water bath for 30min, subpackaging, and storing in-20 deg.C low temperature refrigerator.
③ PBS buffer solution: weighing 8.0g of NaCl, 0.20g of KCl and Na2HPO4·H2O 1.56g、KH2PO4.2.0 g, dissolved in 1000ml of triple distilled water, autoclaved, and stored in a refrigerator at 4 ℃.
(3) Cell growth activity inhibition detection related reagent
MTT powder was purchased from Sigma-Aldrich.
(4) Apoptosis detection related reagent
Annexin V-PI double staining kit was purchased from Kyoto.
1.2 Experimental instruments
(1) YJ-875 type medical purification workbench: suzhou purification plant.
(2)3111 type water jacket CO2An incubator: product of Thermo electron corporation, usa.
(3) An electronic balance: product of Beijing Sidolis Instrument systems, Inc.
(4) QIUJING cytometry plate: shanghai, China.
(5) LD4-2 general centrifuge: beijing medical centrifuge factory products.
(6) Model YG-2000 cylindrical filter: the product of manufacturing company of satellite medical equipment in Shaoxing city.
(7) KY-111 type micro air compressor: the product of manufacturing company of satellite medical equipment in Shaoxing city.
(8) Model 5417R bench refrigerated high speed centrifuge: product of Eppendorf company, germany.
(9) WP type pH pocket test pen: product of the American excel instruments company.
(10) Research type single channel adjustable pipettor: product of Eppendorf company, germany.
(11) Model THZ-312 desk-top thermostat oscillator: shanghai essence macro test equipment Co., Ltd.
(12) Varioskan full-wavelength microplate reader: thermo corporation, usa.
(13) Flow cytometry: becton Dickinson, Inc. in the United states.
1.3 cell lines
Glioma cell line U87 was purchased from Shanghai national academy of sciences. All cells were cultured in MEM containing 100U/ml penicillin, 100mg/ml streptomycin and 10% fetal bovine serum.
Example 1 MTT assay
MTT solution can be reduced into blue-violet crystal formazan by mitochondrial dehydrogenase in living cells, and the DMSO can dissolve the formazan, and the color shade of the formed solution is in direct proportion to the cell activity, so that the cell activity can be detected. Culturing the cells in a 96-well enzyme label plate according to a proper cell density, wherein the volume of the cells in each well is 100 mu l, and meanwhile, 100 mu l of GL-V9 with a specified concentration is added; continuously placing the cells to which the medicine is applied in an incubator for 24 hours, and adding 20 mu l of MTT solution into each hole; after further incubation for 4h, the supernatant was removed, 100. mu.l DMSO was added to each well, the mixture was shaken in a micro-shaker, and after the crystals were completely dissolved, the absorbance was measured at 570 nm. And (3) after the detected light absorption value is finished, calculating the growth inhibition rate of the drug to the cells according to the following formula:
the influence of the natural product derivative GL-V9 on the growth activity of the glioma cell line U87 within 24h is detected by an MTT (methyl thiazolyl tetrazolium) experiment. The experimental results show (figure 1) that GL-V9 can inhibit the growth activity of U87 cells, and the results preliminarily confirm the effect of GL-V9 on resisting brain glioma.
Example 2 Annexin V/PI apoptosis double staining experiment
After the drug acts for a designated time, centrifuging at 2000rpm for 5min, collecting cell suspension, removing the culture medium, washing the cells twice with precooled PBS solution, adding 400 μ L of 1 × Binding Buffer for suspensionCells with a cell density of about 1X 106one/mL. And adding 5 mu L of Annexin V into each group of cell suspension, slightly mixing uniformly, incubating for 15min at the temperature of 2-8 ℃ in the dark, adding 5 mu L of PI, slightly mixing uniformly, incubating for 5min at the temperature of 2-8 ℃ in the dark, and detecting by using a flow cytometer within 1 h.
The effect of natural product derivative GL-V9 on apoptosis of brain glioma cell line U87 at the 24h time point was determined by flow cytometry. The Annexin V/PI double-staining experiment result shows that (figure 2) GL-V9 can remarkably promote early and late apoptosis of U87 cells. This result preliminarily confirmed that GL-V9 exerts an anti-glioma effect by inducing apoptosis of cells.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (4)
1. An application of a flavonoid derivative GL-V9 in preparing medicine for resisting brain glioma is provided.
2. The use according to claim 1, wherein the brain glioma is U87 cells.
3. The use of claim 1 or 2, wherein GL-V9 is capable of inhibiting the growth viability of brain glioma U87 cells.
4. The use of claim 1 or 2, wherein GL-V9 is capable of promoting early and/or late apoptosis in brain glioma U87 cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011522216.6A CN113244228A (en) | 2020-12-21 | 2020-12-21 | Application of GL-V9 in preparation of anti-glioma drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202011522216.6A CN113244228A (en) | 2020-12-21 | 2020-12-21 | Application of GL-V9 in preparation of anti-glioma drug |
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| Publication Number | Publication Date |
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| CN113244228A true CN113244228A (en) | 2021-08-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011522216.6A Pending CN113244228A (en) | 2020-12-21 | 2020-12-21 | Application of GL-V9 in preparation of anti-glioma drug |
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| CN (1) | CN113244228A (en) |
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2020
- 2020-12-21 CN CN202011522216.6A patent/CN113244228A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| 张丽莹等: "高效液相色谱法测定GL-V9的含量和有关物质", 《中南药学》 * |
| 邢晗等: "高抗肿瘤活性汉黄芩素衍生物 GL-V9 在大鼠体内的组织分布和排泄研究", 《中国临床药理学与治疗学》 * |
| 陈望昊等: "汉黄芩素调节恶性胶质瘤U87细胞增殖和凋亡并影响miR-128的表达", 《南京医科大学学报（自然科学版）》 * |
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Application publication date: 20210813 |
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