CN116077496B - Application of shikonin combined with CM-272 in preparation of medicines for treating lung cancer - Google Patents
Application of shikonin combined with CM-272 in preparation of medicines for treating lung cancer Download PDFInfo
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- CN116077496B CN116077496B CN202310084974.1A CN202310084974A CN116077496B CN 116077496 B CN116077496 B CN 116077496B CN 202310084974 A CN202310084974 A CN 202310084974A CN 116077496 B CN116077496 B CN 116077496B
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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Abstract
The invention relates to the technical field of medicine preparation, in particular to application of shikonin combined with CM-272 in preparing medicines for treating lung cancer. The invention provides application of shikonin and CM-272 in preparing medicaments for treating non-small cell lung cancer and designing related treatment schemes, wherein the chemical components can inhibit the growth of non-small cell lung cancer cells and promote the apoptosis of the non-small cell lung cancer cells under a certain concentration, thereby achieving the purpose of treating the non-small cell lung cancer.
Description
Technical Field
The invention relates to the technical field of medicine preparation, in particular to application of shikonin combined with CM-272 in preparing medicines for treating lung cancer.
Background
Lung cancer is a cancer with a high incidence and mortality rate. For cancers with high morbidity, high mortality and low cure rate, a new treatment way is explored, and development of new therapeutic drugs is urgent. Lung cancer is divided into two types: small cell lung cancer and non-small cell lung cancer, wherein the non-small cell lung cancer accounts for 85% and the small cell lung cancer accounts for 15%. It follows that treatment for non-small cell lung cancer is a key point in lung cancer treatment. Through continuous exploration efforts of scientific researchers for many years, the non-small cell lung cancer treatment breaks through greatly in the aspects of radiotherapy, chemotherapy, immune drug treatment, targeted treatment and the like, but the drug resistance caused by drug treatment is unavoidable.
At present, research has proved that the combined treatment is a mature and reliable way for solving the problem of single drug resistance, and can improve the curative effect of the drug and reduce the toxicity of the drug. Therefore, the exploration of the combined treatment scheme of the non-small cell lung cancer brings new thought and direction for clinical medication.
Disclosure of Invention
The invention aims to provide application of shikonin and CM-272 in preparing medicaments for treating non-small cell lung cancer and designing related treatment schemes, and provides new application of the shikonin and CM-272 in preparing medicaments.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an application of shikonin combined with CM-272 in preparing a medicine for treating lung cancer.
Preferably, the lung cancer is non-small cell lung cancer.
Preferably, the volume ratio of shikonin to CM-272 is 4-12:1.
The invention also provides a medicine for treating lung cancer, which comprises shikonin, CM-272 and pharmaceutically acceptable auxiliary materials.
Preferably, the dosage form of the medicament comprises capsules, pills, tablets, granules or injections.
Compared with the prior art, the invention has the following beneficial effects:
1. radix Arnebiae generally refers to root of radix Arnebiae, belongs to a Chinese medicine, and is generally used for treating infection, inflammation and hemorrhagic diseases. Shikonin is the main active ingredient of lithospermum, and recent researches indicate that shikonin has various biological activities and is related to cancer treatment. Shikonin has anticancer activity, but has not been clinically used so far due to toxicity problems. CM-272 is a novel histone methyltransferase 2 (EHMT2) G9a reversible inhibitor, and the research shows that the G9a inhibitor can promote cancer cell apoptosis by regulating PI3K-mTOR-Akt signaling pathway. Because shikonin also has an influence on a PI3K-mTOR-Akt signal pathway, the shikonin and the CM-272 can be used in a combined way to treat non-small cell lung cancer, and the shikonin and the CM-272 are creatively used in a combined way, so that the obtained pharmaceutical composition has an excellent effect of inhibiting the growth of lung cancer cells.
2. The invention provides application of shikonin and CM-272 in preparing medicaments for treating non-small cell lung cancer and designing related treatment schemes, wherein the chemical components can inhibit the growth of non-small cell lung cancer cells and promote the apoptosis of the non-small cell lung cancer cells under a certain concentration, thereby achieving the purpose of treating the non-small cell lung cancer.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only embodiments of the present invention, and that other drawings can be obtained according to the provided drawings without inventive effort for a person skilled in the art.
Fig. 1: effect of shikonin and CM-272 on proliferation of human non-small cell lung cancer cell A549: the shikonin with a certain concentration is acted with CM-272 and non-small cell lung cancer cells for 14 days, and then the relative clone number of the non-small cell lung cancer cells is detected by a semi-quantitative analysis method of microscopic imaging and an enzyme-labeled instrument. The results show that, compared with the control group, the shikonin and the CM-272 both have the inhibition effect on the proliferation of the non-small cell lung cancer cells, and the combined effect of the shikonin and the CM-272 is better than that of the single use; n=3 in each series; p compared to control group<0.01; compared with shikonin group (Shi), ## P<0.01; in contrast to the CM-272 group (CM), ΔΔ P<0.01；
fig. 2: effect of shikonin and CM-272 on apoptosis of human non-small cell lung cancer cell A549: shikonin with a certain concentration is acted on CM-272 and non-small cell lung cancer cells for 24 hours, and then apoptosis of the non-small cell lung cancer cells is detected by an analytical method of Annexin V-FITC and PI staining. The results show that the shikonin and the CM-272 can promote apoptosis of non-small cell lung cancer cells, and the combined effect of the shikonin and the CM-272 is better than that of single use; apoptotic cells are indicated by the arrows; a: control. B: shikonin. C: CM-272.D: shikonin+CM-272.
Fig. 3: influence of shikonin and CM-272 on apoptosis-related proteins of human non-small cell lung cancer cells A549: the shikonin with a certain concentration acts on CM-272 and non-small cell lung cancer cells for 24 hours, and then the expression of apoptosis related proteins Bax, bcl-2, clearedcaspase-8 and cyto-c of A549 cells is carried out by a WesternBlot analysis method, and the result shows that compared with a control group, the shikonin and the CM-272 both enable the expression of clearedcaspase-8 and cyto-c to be increased, and the ratio of Bax/Bcl-2 to be reduced, so that the shikonin and the CM-272 both promote the apoptosis of non-small cell lung cancer cells A549; compared with shikonin group and CM-272 group, the combination drug group has raised clear caspase-8 and cyto-c expression and lowered Bax/Bcl-2 ratio, which shows that the combination drug group has stronger capability of promoting apoptosis of non-small cell lung cancer cells A549; compared with the control group, P<0.05，**P<0.01; compared with shikonin group (Shi), ## P<0.01; in contrast to the CM-272 group (CM), ΔΔ P<0.01。
Detailed Description
The invention provides application of shikonin (S8279, U.S. Selleck Chemicals) and CM-272 (S8812, U.S. Selleck Chemicals) in preparation of medicaments for treating non-small cell lung cancer.
In the invention, the volume ratio of shikonin to CM-272 is 4-12:1; preferably 6-10:1; further preferably 8:1.
The invention also provides a medicine for treating lung cancer, which comprises shikonin, CM-272 and pharmaceutically acceptable auxiliary materials.
In the present invention, the dosage form of the drug preferably includes a capsule, a pill, a tablet, a granule or an injection.
The content of shikonin and CM-272 in the medicine and the adopted auxiliary materials and the auxiliary material content are not particularly limited, the auxiliary materials used for preparing various dosage forms conventionally and the auxiliary material dosage are adopted, and the content of active substances conventionally contained in various dosage forms is adopted.
The preparation method of the medicine is not particularly limited, and the medicine can be prepared by adopting a conventional preparation method of a conventional dosage form.
The invention also provides application of shikonin and CM-272 in designing a drug regimen for treating non-small cell lung cancer.
In the present invention, the dosage form of the drug preferably includes a capsule, a pill, a tablet, a granule or an injection.
The content of shikonin and CM-272 in the medicine and the adopted auxiliary materials and the auxiliary material content are not particularly limited, the auxiliary materials used for preparing various dosage forms conventionally and the auxiliary material dosage are adopted, and the content of active substances conventionally contained in various dosage forms is adopted.
The preparation method of the medicine is not particularly limited, and the medicine can be prepared by adopting a conventional preparation method of a conventional dosage form.
The application method of the medicine is not particularly limited, and the medicine can be used according to the doctor's advice.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
Effect of shikonin and CM-272 on proliferation of human non-small cell lung cancer cell A549
Selecting non-small cell lung cancer cell A549, culturing in vitro with DMEM medium containing 10% Fetal Bovine Serum (FBS) for 24 hr, and adding shikonin 0.4 μmol.L -1 ，CM-2720.05μmol·L -1 shikonin+CM-272 (0.4+0.05) μmol.L -1 The control group was added with medium and allowed to act on cells in vitro for 14 days, photographed by crystal violet staining and analyzed semi-quantitatively for cell proliferation using an enzyme-labeled instrument. The results show (see figure 1) that, compared with the control group, both shikonin and CM-272 have inhibition effect on the proliferation of non-small cell lung cancer cells, and the combined effect of the shikonin and the CM-272 is better than that of the shikonin alone; n=3 in each series; p compared to control group<0.01; compared with shikonin group (Shi), ## P<0.01; in contrast to the CM-272 group (CM), ΔΔ P<0.01；
example 2
Effect of shikonin and CM-272 on apoptosis of human non-small cell lung cancer cell A549
Selecting non-small cell lung cancer cell A549, culturing in vitro culture medium for 24 hr, and adding shikonin 2 μmol.L -1 ，CM-2720.25μmol·L -1 shikonin+CM-272 (2+0.25) μmol.L -1 Adding a culture medium into a control group, reacting with cells in vitro for 24 hours, collecting cells, adding Annexin V-FITC and PI for staining, and performing fluorescence shooting to analyze the apoptosis condition of the cells; the cell proteins were extracted and the apoptosis-related proteins were analyzed for changes in expression by western blot. The results show (see fig. 2 and 3) that alkannin and CM-272 can promote apoptosis of non-small cell lung cancer cells, and the combined effect of the alkannin and CM-272 is better than that of single use; apoptotic cells are indicated by the arrows; control. B, shikonin. C, CM-272.D, shikonin+CM-272; compared with the control group, P<0.05，**P<0.01; compared with shikonin group (Shi), ## P<0.01; in contrast to the CM-272 group (CM), ΔΔ P<0.01；
these results show that shikonin and CM-272 can obviously inhibit proliferation and promote apoptosis of non-small cell lung cancer cell A549, and the combination effect of shikonin and CM-272 is better, and the shikonin and CM-272 are feasible as drug selection and treatment scheme selection for treating non-small cell lung cancer.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (4)
1. Application of shikonin in combination with CM-272 in preparing medicine for treating lung cancer is provided.
2. The use according to claim 1, wherein the lung cancer is non-small cell lung cancer.
3. A medicine for treating lung cancer comprises shikonin, CM-272 and pharmaceutically acceptable adjuvants.
4. A medicament according to claim 3, wherein the dosage form of the medicament comprises a capsule, a pill, a tablet, a granule or an injection.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107137384A (en) * | 2017-06-02 | 2017-09-08 | 广州中医药大学 | Application of the alkannin in treatment lung-cancer medicament is prepared |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107137384A (en) * | 2017-06-02 | 2017-09-08 | 广州中医药大学 | Application of the alkannin in treatment lung-cancer medicament is prepared |
Non-Patent Citations (1)
| Title |
|---|
| 组蛋白甲基转移酶G9a抑制剂的研究进展;王楚慧;赵铜鑫;陈维琳;湛云鹏;张涵煦;尤启冬;郭小可;;药学进展(第04期);284-293 * |
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