阅读说明：本技术 萘哌地尔联用2-Deoxy-D-glucose在制备治疗胰腺癌药物中的应用 (Application of naftopidil combined 2-Deoxy-D-glucose in preparation of medicine for treating pancreatic cancer ) 是由 朱志远 刘聪聪 于 2020-12-28 设计创作，主要内容包括：本发明揭露萘哌地尔联用2-Deoxy-D-glucose在制备治疗胰腺癌药物中的应用,萘哌地尔联合2-Deoxy-D-glucose后具有明显的胰腺癌细胞活力抑制作用,细胞活力抑制率达到了95％。其联合形成的药物具有治疗胰腺癌的效果。(The invention discloses application of naftopidil in combination with 2-Deoxy-D-glucose in preparation of a medicine for treating pancreatic cancer, wherein the naftopidil has an obvious effect of inhibiting pancreatic cancer cell activity after being combined with the 2-Deoxy-D-glucose, and the cell activity inhibition rate reaches 95%. The combined medicine has the effect of treating pancreatic cancer.)

1. Application of naftopidil in combination with 2-Deoxy-D-glucose in preparation of medicines for treating pancreatic cancer.

2. An application of naftopidil and 2-Deoxy-D-glucose in preparing the medicines for treating pancreatic cancer.

3. A medicament for treating pancreatic cancer, characterized by: the medicine contains naftopidil and 2-Deoxy-D-glucose.

Technical Field

The invention relates to the field of pharmacotherapeutics, in particular to application of naftopidil combined 2-Deoxy-D-glucose in preparation of a medicament for treating pancreatic cancer.

Background

Pancreatic cancer is called ' Wan ' cancer king ' and is a digestive tract malignant tumor with high malignancy and difficult diagnosis and treatment, the disease process is rapid and the prognosis is poor, the 5-year survival rate is less than 1%, and the relative mortality rate is the first of ten major malignant tumors. Meanwhile, the treatment only adopts one means of surgical treatment, and all the existing medicines have no ideal effect. Although the incidence of pancreatic cancer accounts for only about 3% of new cancers, the number of patients who die of pancreatic cancer in developed countries is 4 th in malignant tumors and 6 th in China. It is expected that by 2030, pancreatic cancer will surpass breast, prostate and colon cancers, being the second to approximately death cancer next to lung cancer.

The most effective treatment for pancreatic cancer is surgical resection, but more than 50% of pancreatic cancers have been diagnosed with significant distant metastasis and are not suitable for surgical resection. At present, the pancreatic cancer is mainly treated by gemcitabine, and in addition, a plurality of gemcitabine and other drugs are combined for treatment, such as gemcitabine + carboplatin, gemcitabine + capecitabine and the like, but the pancreatic cancer treatment effect is far from the expectation. Therefore, the development of a new pancreatic cancer treatment scheme is of great significance, and research for several years finds that the drug combination treatment of tumors breaks through the treatment of various tumors.

Naftopidil (Naftopidil) is a novel long-acting and high-selectivity alpha 1-receptor blocker, and is mainly used for treating urination disorders caused by prostatic hyperplasia clinically at present. At present, the naftopidil has research reports that naftopidil has the effect of treating tumors such as prostate cancer, bladder cancer, gastric cancer and the like. 2-Deoxy-D-glucose (2-DG) is a glucose analog that is an inhibitor of glucose metabolism by acting on hexokinase (hexokinase) to inhibit glycolysis. To date, the effect of naftopidil in combination with 2-Deoxy-D-glucose in the treatment of pancreatic cancer has likewise not been reported.

Disclosure of Invention

The invention aims to provide application of naftopidil combined 2-Deoxy-D-glucose in preparation of a medicine for treating pancreatic cancer.

The invention discloses an application of naftopidil in combination with 2-Deoxy-D-glucose in preparation of a medicine for treating pancreatic cancer.

The invention discloses an application of a naftopidil and 2-Deoxy-D-glucose drug composition in preparing a drug for treating pancreatic cancer.

The invention discloses a medicament for treating pancreatic cancer, which has naftopidil and 2-Deoxy-D-glucose.

The invention has the effective effects that the naftopidil combined with 2-Deoxy-D-glucose has obvious effect of inhibiting the activity of pancreatic cancer cells, and the inhibition rate of the cell activity reaches 95%. The combined medicine has the effect of treating pancreatic cancer.

Drawings

FIG. 1 is a graph showing the effect of naftopidil (20. mu.M) on the inhibition of pancreatic cancer cell activity by human pancreatic cancer cells (PANC-1 cells), 2-Deoxy-D-glucose (1mM) on human pancreatic cancer cells (PANC-1 cells), naftopidil (20. mu.M) in combination with 2-Deoxy-D-glucose (1 mM).

FIG. 2 is a graph showing the effect of naftopidil in combination with 2-Deoxy-D-glucose in inhibiting pancreatic cancer tumor growth. Graph of the effect of naftopidil in combination with 2-Deoxy-D-glucose in reducing the size of pancreatic cancer.

Detailed Description

The invention will be further illustrated with reference to specific examples, which should not be construed as limiting the inventive concept.

The invention relates to an application of naftopidil combined 2-Deoxy-D-glucose in preparing a medicament for treating pancreatic cancer.

The invention relates to an application of a naftopidil and 2-Deoxy-D-glucose drug composition in preparing a drug for treating pancreatic cancer.

The invention relates to a medicament for treating pancreatic cancer, which contains naftopidil and 2-Deoxy-D-glucose.

Example 1: nappeidil combined 2-Deoxy-D-glucose for inhibiting activity of pancreatic cancer cells

The invention detects the inhibition effect of naftopidil or 2-Deoxy-D-glucose and the combined use of naftopidil and 2-Deoxy-D-glucose on the activity of pancreatic cancer cells (PANC-1) in human pancreatic cancer cell strains (PANC-1) through an MTT (methyl thiazolyl tetrazolium) experiment. The result shows that both 2-Deoxy-D-glucose and naftopidil can only slightly inhibit the activity of pancreatic cancer cells, and the naftopidil combined with 2-Deoxy-D-glucose has obvious effect of inhibiting the activity of pancreatic cancer cells.

1. Principle of experiment

Thiazole blue (3- (4, 5-dimethylthiazole-2) -2, 5-diphenyltetrazolium bromide, 3- (4,5) -dimethylhiazolo (-z-y1) -3, 5-di-phenyltetrazolium amide, MTT) can be reduced by succinate dehydrogenase to crystalline Formazan (Formazan) in living cell mitochondria and then solubilized by dimethyl sulfoxide (DMSO) to purple Formazan, which has significant light absorption at OD490 wavelengths, whereas mitochondria in dead cells do not. Therefore, the light absorption value can be measured by a microplate reader at 490nm wavelength, and the OD490 light absorption value is proportional to the number of living cells in a certain cell number range. Thus, the effect of a compound on cell viability can be detected by the MTT assay.

2. Experimental materials and methods

1) Cell culture reagents were purchased from Gibico, DMSO from Sigma, and MTT from Shanghai bioengineering, Inc.

2) MTT test: PANC-1 cells are inoculated in a 96-well plate at 3000 cells per well, the compound naftopidil (20 mu M), 2-Deoxy-D-glucose (1mM) or naftopidil (20 mu M) +2-Deoxy-D-glucose (1mM) is respectively added into a cell culture solution, the compound is incubated for 3 days, and then the cell viability is detected by an MTT experiment. MTT was formulated at 5mg/ml, 10. mu.L was added to each well, incubation was continued for 4 hours, then the culture was aspirated, 100. mu.L of DMSO was added to each well, dissolution was performed with shaking for 10 minutes, then the light absorption value was measured at 490nM by a microplate reader, and then the IC50 value of the compound against PANC-1 cell inhibition was calculated.

3. Results of the experiment

The results are shown in figure 1, naftopidil (20 μ M) has no inhibiting effect on human pancreatic cancer cells (PANC-1 cells) basically, 2-Deoxy-D-glucose (1mM) has no inhibiting effect on human pancreatic cancer cells (PANC-1 cells) at the same time, but naftopidil (20 μ M) has obvious inhibiting effect on pancreatic cancer cell viability after being combined with 2-Deoxy-D-glucose (1mM), and the cell viability inhibiting rate reaches 95%.

Example 2: the naftopidil combined with 2-Deoxy-D-glucose has the effect of obviously inhibiting the growth of pancreatic cancer tumors.

1. Principle of experiment

The Nude mouse is a athymic mouse, and the reduction of the immunity of the Nude mouse is suitable for a xenogenesis inhibition experiment of human tumor cells. In the experiment, human pancreatic cancer cells (PANC-1 cells) are inoculated subcutaneously into Nude mice to form xenogeneic inoculation of human tumor cells. And then evaluating the antitumor activity of the compound by detecting the index evaluation of the tumor volume.

2. Experimental methods and materials

1) Experimental animals:

30 nude mice are transplanted subcutaneously with PANC-1 cells, 20 mice successfully molded with nude mice tumor volume of 200-300mm3 are selected after 10-15 days, the mice are randomly grouped according to the tumor volume, the average value difference of the tumor volume of each group of mice is small, the statistical significance is avoided, and the SD value of the tumor volume of the mice between the groups is less than 1/3 of the average value.

2) Experimental materials:

naftopidil and 2-Deoxy-D-glucose are purchased from Shanghai Bigdi medicine science and technology Limited, and cell culture reagents such as DMEM culture solution, calf embryo serum, PS and the like are purchased from Gibico.

3) The experimental method comprises the following steps:

the experiment adopts a subcutaneous tumor model of human pancreatic cancer PANC-1 cells, after the PANC-1 cells are cultured and expanded, 5 × 106/mouse is inoculated under the skin of a nude mouse, then the growth condition of subcutaneous tumor is monitored every three days, 20 successful molded mice with the tumor volume of 200-300mm3 of the nude mouse are selected after 10-15 days and are randomly divided into 2 groups, 10 mice in each group meet the condition that the average value difference of the tumor volume of each group of mice is small, the statistical significance is avoided, and the SD value of the tumor volume of the mice in the groups is less than 1/3 of the average value. After grouping, intraperitoneal injections of different compounds (solvent group, naftopidil (20mg/kg/day) +2-Deoxy-D-glucose (100mg/kg/day)) were started for 3 weeks, during which tumor volumes were monitored every three days. The therapeutic effect of the drug on tumors was evaluated by tumor size.

4) Results of the experiment

The result is shown in figure 2, which shows that the naftopidil combined 2-Deoxy-D-glucose can obviously reduce the size of pancreatic cancer, and that the naftopidil combined 2-Deoxy-D-glucose has a high-efficiency pancreatic cancer resistance effect.

The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes, or direct or indirect applications in other related fields, which are made by the contents of the present specification, are included in the scope of the present invention.