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Application of energy metabolism-interfering drug in recurrence of pancreatic cancer

A technology of drugs and medicinal salts, which is applied in the fields of medicine, biology, pancreatic cancer recurrence and its treatment, and can solve the problems of joint application without reports

Inactive Publication Date: 2018-04-10
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the combined application of carboxytriazole and 2-deoxyglucose has not been reported

Method used

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  • Application of energy metabolism-interfering drug in recurrence of pancreatic cancer
  • Application of energy metabolism-interfering drug in recurrence of pancreatic cancer
  • Application of energy metabolism-interfering drug in recurrence of pancreatic cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Example 1: Inhibitory Effect of CAI on Mitochondrial Oxygen Consumption of Pancreatic Cancer Stem Cells.

[0065] Human pancreatic cancer Panc-1 cells were seeded in serum-free DMEM supplemented with 0.4% bovine serum albumin, 20ng / mL epidermal growth factor, 10ng / mL basic fibroblast growth factor and insulin-transferrin-selenium (100×) In culture medium, the density is 1000 cells / mL.

[0066] Add 10 mL of cell suspension to the T25 culture flask and place it vertically.

[0067] After 15 days, the Panc-1 stem cell spheres formed in the culture medium were collected, digested with Accutase, resuspended, and inoculated in a specific cell plate used for Seahorse bioenergy measurement, with 10,000 cells per well.

[0068] After the cells were inoculated overnight, the cell culture medium was replaced with the Seahorse detection working solution with the minimum buffer capacity (1mM pyruvate, 2mM glutamine and 10mM glucose, pH 7.4), and the basic oxygen consumption rate (O...

Embodiment 2

[0070] Example 2: Inhibitory effect of CAI and 2-DG on self-renewal of pancreatic cancer stem cell spheroids.

[0071] Human pancreatic cancer Panc-1 cells were seeded in serum-free DMEM supplemented with 0.4% bovine serum albumin, 20ng / mL epidermal growth factor, 10ng / mL basic fibroblast growth factor and insulin-transferrin-selenium (100×) In culture medium, the density is 1000 cells / mL.

[0072] Add 10 mL of cell suspension to the T25 culture flask and place it vertically.

[0073] After 15 days, the Panc-1 stem cell spheres formed in the culture medium were collected, digested with Accutase, resuspended, and counted.

[0074] Adjust the density again to 1000 cells / mL, add 9 mL of cell suspension to the T25 culture flask, and then add 1 mL of 10× drug solution (1% DMSO as solvent control (CON), or 100 μM CAI, or 10 mM 2-DG , or 100μM CAI and 10mM 2-DG were added together), placed vertically.

[0075] After 15 days, the Panc-1 stem cell spheres formed in the culture mediu...

Embodiment 3

[0077] Example 3: The combination of CAI and 2-DG in vivo significantly inhibited the growth of pancreatic cancer after gemcitabine treatment

[0078] Human pancreatic cancer Panc-1 cells were inoculated in the right axilla of Balb / c nude mice at a density of 2×10 6 cells / only.

[0079] Tumor volume up to 1000mm 3 , randomly grouped and given different drug treatments:

[0080] - The solvent control group (CON) is polyethylene glycol PEG 400, 0.1ml / 10g body weight, administered by intragastric administration;

[0081] - Gemcitabine group: 80mg / kg, 0.1ml / 10g body weight, intraperitoneal injection;

[0082] - Gemcitabine and CAI combined group, gemcitabine dosage and method are the same as single use group, CAI is 20mg / kg, 0.1ml / 10g body weight, intragastric administration;

[0083] - Gemcitabine, CAI and 2-DG combined group, the dosage and method of gemcitabine and CAI are the same as the previous group, 2-DG is 450mg / kg, 0.1ml / 10g body weight, administered by intraperitone...

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Abstract

The invention relates to an application of an energy metabolism-interfering drug in recurrence of pancreatic cancer. Specifically, the invention discloses a pharmaceutical composition which comprisescarboxyamidotriazole or a pharmaceutically acceptable salt thereof and a glycolytic inhibitor. Carboxyamidotriazole and the glycolysis inhibitor are used for blocking from oxidative phosphorylation and glycolysis ways respectively, so the content of ATP in cells can be significantly reduced, the vitality and self renewal of pancreatic cancer stem cells are seriously destroyed, and thus the recurrence of pancreatic cancer after drug treatment can be delayed.

Description

technical field [0001] The present disclosure relates to the fields of medicine and biology, especially the recurrence of pancreatic cancer and its treatment. Background technique [0002] The prognosis of pancreatic cancer is extremely poor, with a 5-year survival rate of less than 10%, and it is known as the "king of cancer". Most patients are diagnosed at an advanced stage and may be asymptomatic before that. About 20% of patients can undergo surgical resection after diagnosis, but even if they undergo radical resection, these patients may experience recurrence of pancreatic cancer, and their 5-year survival rate is only about 25%. [0003] Gemcitabine is a cytotoxic drug that inhibits DNA synthesis and is currently one of the first-line treatments for pancreatic cancer. Six courses of adjuvant chemotherapy with gemcitabine after surgery resulted in longer progression-free survival and overall survival than those who did not receive gemcitabine chemotherapy. However, t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4192A61K31/7004A61K45/06A61P35/00
CPCA61K31/4192A61K31/7004A61K45/06A61K2300/00
Inventor 鞠瑞叶菜英张德昌郭磊
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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