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Application of canagliflozin in treatment of pancreatic cancer

A technology for pancreatic cancer and drugs, which is applied in the field of preparation of drugs for treating pancreatic cancer, can solve problems such as adverse reactions and allergic reactions, achieve the effects of inhibiting glycolysis, inhibiting apoptosis, and good clinical application prospects

Pending Publication Date: 2020-09-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date, radical resection is still the first choice for the treatment of patients with pancreatic cancer, but since most patients are detected at an advanced stage, less than 15% of patients have the opportunity to undergo radical resection
Gemcitabine is the drug of choice for the treatment of pancreatic cancer, which prolongs the survival of patients for several months, but is accompanied by many adverse reactions, such as nephrotoxicity, allergic reactions, edema, atrophy of hematopoietic organs, and immunosuppression

Method used

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  • Application of canagliflozin in treatment of pancreatic cancer
  • Application of canagliflozin in treatment of pancreatic cancer
  • Application of canagliflozin in treatment of pancreatic cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Antitumor activity of canagliflozin against pancreatic cancer cells:

[0039] 1. Solution preparation

[0040] (1) Canagliflozin solution: weigh canagliflozin raw material, dissolve in 1mL DMSO, and prepare 80mmol / L mother solution, pass through a 0.22μm microporous membrane, filter and sterilize, and then dispense into multiple 200μL EP tubes were stored in a -20°C refrigerator for later use.

[0041] (2) DMEM medium: take DMEM medium freeze-dried powder, dissolve in 1L double distilled water, stir magnetically, add about 1.6g sodium bicarbonate, adjust the pH of the solution to 7.2, pass through a 0.22μm filter membrane in a sterile environment Sterilize by filtration and store at 4°C until use. When culturing the cells, 10% Gibco fetal bovine serum and 100 U / mL penicillin-streptomycin were added to the culture medium.

[0042] (3) Trypsin: weigh 4.0g of NaCl, 0.1g of KCl, NaCl 2 HPO 4 12H 2 O 1.45g, KH 2 PO 4 Dissolve 0.1g in 400mL of double-distilled water,...

Embodiment 2

[0072] Antitumor activity of canagliflozin on pancreatic cancer tumor-bearing mice:

[0073] 1. Establishment of pancreatic cancer PANC-1 tumor-bearing mouse xenograft model

[0074] Balb / c male mice were kept in the animal experiment center of China Pharmaceutical University with a temperature of 22±1°C and 12 hours of light per day, providing them with sufficient food and water, and the animal experiment operations followed the animal ethics of China Pharmaceutical University committee. Take PANC-1 cells in good growth state and in the logarithmic growth phase, digest the cells, wash with normal saline three times, wash off the residual medium on the cell surface, add normal saline, and suspend evenly. By counting, adjust the PANC-1 cell density to 6 × 10 6 individual / mL. Inject 100 μL of cell suspension under the armpit of each nude mouse, and after one week, the tumor grows to about 80-100 mm 3 At the same time, the Balb / c male nude mice were randomly divided into 6 gr...

Embodiment 3

[0083] Canagliflozin inhibits glycolysis in pancreatic cancer cells:

[0084] 1. Glucose uptake experiment

[0085] Glucose content was detected by a glucose kit. Experimental principle: Glucose in the sample can be oxidized by glucose oxidase into gluconic acid and hydrogen peroxide, and hydrogen peroxide can couple the reduced 4-aminoantipyrine to phenol under the catalysis of peroxidase Condensation into quinone compounds that can be measured by spectrophotometer. Place the culture plate with the cells in an incubator for culture. After it adheres to the wall, add canagliflozin to treat it. Take out the cell supernatant at 6h, 12h and 24h after administration, add the working solution and mix thoroughly. Put the sample tube into the spectrophotometer whose OD value is adjusted to 505nm wavelength, measure the absorbance value of each sample tube, and finally record the data and process the result.

[0086] Depend on Figure 12 and Figure 13 As shown, the glucose uptak...

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Abstract

The invention discloses an application of canagliflozin in treatment of pancreatic cancer. The chemical name of the canagliflozin is (1S)-1,5-dehydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl] methyl]-4-methylphenyl]-D-glucitol. A pancreatic cancer tumor cell model and a mouse pancreatic cancer transplantation tumor model are utilized to find that canagliflozin can obviously inhibit the growth and proliferation of pancreatic cancer cells Capan-1 and PANC-1; meanwhile, canagliflozin can inhibit migration of tumor cells; in addition, researches find that canagliflozin can interfere pancreatic cancercell glycolysis related metabolic functions and induce apoptosis of pancreatic cancer cells. The tumor volume of pancreatic cancer subcutaneous transplantation tumor PANC-1 of tumor-bearing mice subjected to canagliflozin treatment is obviously reduced. Therefore, canagliflozin has a bright application prospect in clinical treatment of pancreatic cancer.

Description

technical field [0001] The present invention relates to the application of a kind of medicine, specifically canagliflozin (chemical name: (1S)-1,5-dehydro-1-C-[3-[[5-(4-fluorophenyl)-2 -Thienyl] methyl] -4-methylphenyl] -D-glucitol, English name: Canagliflozin, CANA) anti-pancreatic cancer application in the preparation of drugs for the treatment of pancreatic cancer. Background technique [0002] Pancreatic cancer, the most common solid malignancy, is characterized by insidious clinical symptoms, rapid progression, and poor prognosis, which may be due to low angiogenesis, marked fibrotic stromal response, genomic complexity, and metabolic alterations. Pancreatic cancer's poor survival rate is largely due to its anatomically unique location that precludes routine testing, so patients are diagnosed at an advanced stage. So far, radical resection is still the first choice for the treatment of patients with pancreatic cancer, but because most patients are found at an advanced ...

Claims

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Application Information

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IPC IPC(8): A61K31/381A61K31/7068A61P1/18A61P35/00
CPCA61K31/381A61K31/7068A61P1/18A61P35/00A61K2300/00
Inventor 周长林何良愿许世霖庞树洋徐兑悦
Owner CHINA PHARM UNIV
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