CN113209149A

CN113209149A - Application of mitoxantrone and total ginsenoside combined medicine in preparation of medicine for treating gastric cancer

Info

Publication number: CN113209149A
Application number: CN202010577970.3A
Authority: CN
Inventors: 李斌
Original assignee: Alpha Cat Hangzhou Artificial Intelligence Biotechnology Co ltd
Current assignee: Alpha Cat Hangzhou Artificial Intelligence Biotechnology Co ltd
Priority date: 2020-06-23
Filing date: 2020-06-23
Publication date: 2021-08-06

Abstract

The invention belongs to the field of medicines, and particularly relates to application of mitoxantrone and total ginsenoside combined medicine in preparation of a medicine for treating gastric cancer. The invention firstly provides the application of the mitoxantrone and total ginsenoside combined medicine in preparing the medicine for treating gastric cancer, the mitoxantrone and the total ginsenoside have obvious synergistic effect, the curative effect is effectively improved, the curative effect is more obvious compared with that of a single component, and the killing property to tumor cells is improved; effectively reduces the dosage, thereby reducing the toxic and side effects. The combined use of the two can also save the cost, reduce the economic burden of patients, provide a new way for preventing and treating gastric cancer, and have wide application prospect in the field of medicine and pharmacology.

Description

Application of mitoxantrone and total ginsenoside combined medicine in preparation of medicine for treating gastric cancer

The technical field is as follows:

the invention belongs to the field of medicines, and particularly relates to application of mitoxantrone and total ginsenoside combined medicine in preparation of a medicine for treating gastric cancer.

Background art:

gastric cancer is a common malignant tumor of the digestive tract, ranks third in the cancer-related deaths worldwide, and is one of the main health burdens of society. In China, gastric cancer is the second most prevalent cancer and the second leading cause of cancer death, so the development of anti-gastric cancer drugs is the hot spot of anti-tumor research and development in China. At present, the main treatment means of the gastric cancer is chemotherapy, but the single chemotherapy curative effect of the gastric cancer is poor, and the median survival time is only 8-13 months.

Mitoxantrone is a new anthraquinone antitumor drug, has similar structure and anticancer effect to adriamycin, and has low toxicity to heart because of no amino sugar structure, no free radical generation, and lipid peroxidation inhibition. The action mechanism shows that mitoxantrone is a cell cycle nonspecific drug, and can kill cancer cells in any cell cycle, so that proliferation and non-proliferation cells are inhibited. The antitumor activity of the compound is equivalent to or slightly higher than that of adriamycin, and is obviously higher than that of cyclophosphamide, fluorouracil, methotrexate, vincristine and cytarabine, the compound has a wide antitumor spectrum, and the compound has a synergistic effect with a plurality of common antitumor drugs.

The total saponins of Ginseng radix are total saponins extracted from root of Panax ginseng C.A. Meyer of Araliaceae. The ginsenoside can enhance immunity, relieve side effects of chemotherapy for cancer patients and patients with weak constitution, enhance anti-tumor ability, and effectively prevent cancer, and the main components of the ginsenoside can prevent cancer cell formation and accelerate metabolism to achieve anti-tumor effect. The cancer cells are not easy to relapse after long-term administration, and the cancer cell metastasis inhibiting effect is obvious.

Reports on the combined action effect of the mitoxantrone and the ginseng total saponins do not appear yet. The invention researches the effect of the mitoxantrone and total ginsenoside combined drug in treating gastric cancer in a mouse pdx model.

The invention content is as follows:

object of the Invention

The function of the mitoxantrone and the total ginsenoside in preparing the medicine for treating gastric cancer is provided, so that the anti-tumor curative effect is obviously enhanced, and a basis is provided for new application of old medicines.

Technical scheme

The invention provides application of a mitoxantrone and total ginsenoside combined medicine in preparing a medicine for treating gastric cancer.

Therefore, the application of the mitoxantrone and the ginseng total saponin in the aspect of preparing the anti-gastric cancer medicament and the anti-gastric cancer medicament simultaneously containing the mitoxantrone and the ginseng total saponin are all within the protection scope of the invention.

Preferably, the dosage ratio of the mitoxantrone to the total ginsenoside is 3 mg/kg: 9 mg/kg.

Advantageous effects

The invention discloses the discovery of the combined medication of the mitoxantrone and the total ginsenoside on the aspect of inhibiting gastric cancer tumors for the first time, can realize the synergistic effect, realize the obvious improvement of the anti-tumor effect, and reduce the dosage of the mitoxantrone and the total ginsenoside through the combined medication so as to reduce the toxic and side effect, thereby having obvious significance on the application of the combined medication of the mitoxantrone and the total ginsenoside on the aspect of resisting gastric cancer.

Description of the drawings:

FIG. 1 is a graph showing the volume increase of transplanted tumors in experimental mice.

FIG. 2 is the results of HE staining of tumor histopathology following administration of different drugs.

The specific implementation mode is as follows:

the invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.

Example 1 mouse pdx model establishment

First, experimental material

Matrigel Matrix gel (Corning, usa), RPMI 1640 medium (Biological Industries, israel), human MGC803 cells from gastric cancer.

Secondly, tumor cell inoculation

1. MGC803 cells are cultured until the confluence degree reaches about 80%, and the cells are digested by pancreatin and collected.

2. The collected cells were gently flushed 2 times with PBS in order to remove cell surface serum proteins.

3. Suspending in serum-free medium, adjusting cell concentration to 20 × 10⁷And/ml, 100 microliter of cell sap is injected subcutaneously into the right flank of each nude mouse, namely 200 ten thousand MGC803 tumor cells are injected subcutaneously into each nude mouse.

4. After 1-2 weeks, the tumor cells stably grow under the skin of the nude mice, tumor bodies are formed, the nude mice with proper tumor body sizes are picked, randomly grouped, and the administration is started according to requirements.

Example 2 mouse graft volume Change

First, experiment grouping

1. Blank group: no drug was administered.

2. Mitoxantrone group: mitoxantrone was administered at 3mg/kg, once by intravenous injection.

3. The total ginsenoside group: administering 9mg/kg of total ginsenoside once by intragastric administration.

4. A combination of drugs: mitoxantrone was administered by intravenous injection at 3mg/kg once; the total ginsenoside is administered by intragastric administration at a dose of 9 mg/kg.

Second, result analysis

Tumor size was measured before the start of dosing, and every 2 days thereafter until the end of the experiment. The mice were sacrificed the next day after the dosing was completed by vertebration, and the subcutaneous tumor tissue was dissected and photographed.

TABLE 1 volume Change of transplanted tumors in groups of mice

Group of	Day 0 (mm)³）	Day 2 (mm)³）
			Blank group	61.49	129.79
Mitoxantrone group	52.59	70.67
			Ginseng radix total saponin group	55.20	66.44
Combination drug group	36.76	39.47

According to the results shown in fig. 1, the volume growth rate of the transplanted tumor is significantly lower in the mitoxantrone and total ginsenoside combination group than in the other three groups, and it can be known from the above that the mitoxantrone and total ginsenoside combination has significant effect on inhibiting gastric cancer cells.

Example 3 tumor pathology HE staining

One, HE staining

Fixing the dissected subcutaneous tumor tissue with a fixing solution, and preparing a paraffin section. Dewaxing for 3 minutes according to xylene I, II and III respectively, dewaxing for 2 minutes according to absolute ethyl alcohol I, II, 1 minute according to 95% ethyl alcohol, 90% ethyl alcohol and 80% ethyl alcohol respectively, staining with hematoxylin for 10 minutes, differentiating for 15 seconds according to 1% hydrochloric acid alcohol after water washing, soaking in water for 10 minutes, staining with eosin for 3 minutes, 10 seconds according to 80% ethyl alcohol and 90% ethyl alcohol respectively, 1-2 minutes according to 95% ethyl alcohol, 3 minutes according to absolute ethyl alcohol I, II and III respectively, 3 minutes according to xylene I, II and III respectively, finally sealing with neutral gum, and taking a picture under a microscope.

Second, result analysis

As can be seen from the staining results shown in FIG. 2, the blank group, mitoxantrone group and ginsenoside group had significantly deeper tumor cell nuclei, large nuclear-to-cytoplasmic ratio, irregular shape, and densely arranged tumor cells; the combined medicine group has shallow nuclear staining, loose tumor cell arrangement and more necrotic areas. Therefore, the effect of the mitoxantrone and the total ginsenoside combined drug on inhibiting gastric cancer cells is obvious.

Claims

1. Application of mitoxantrone and total ginsenoside in preparing medicine for treating gastric cancer is provided.

2. Use according to claim 1, characterized in that: the dosage ratio of the mitoxantrone to the total ginsenoside is 3 mg/kg: 9 mg/kg.

3. A preparation for treating gastric cancer is characterized in that: the composition consists of the composition as claimed in claims 1-2 and pharmaceutically acceptable auxiliary materials.

4. The formulation of claim 3, for the treatment of gastric cancer, characterized by: the preparation is in the form of injection, tablet, granule or capsule.