Application of composition containing fructose-1,6-bisphosphate in preparation of antitumor drugs

A technology of anti-tumor drugs and compositions, applied in the direction of anti-tumor drugs, medical preparations containing active ingredients, drug combinations, etc., which can solve the problems of toxic and side effects, inability to produce broad-spectrum anti-cancer effects, etc.

Active Publication Date: 2017-11-24
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, inhibition of glycolysis, metabolic utilization of glutamine, mitochondrial oxidative phosphorylation, GDH and NAD+ synthesis, respectively, failed to produce significant broad-spectrum anticancer effects or produce significant toxic side effects

Method used

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  • Application of composition containing fructose-1,6-bisphosphate in preparation of antitumor drugs
  • Application of composition containing fructose-1,6-bisphosphate in preparation of antitumor drugs
  • Application of composition containing fructose-1,6-bisphosphate in preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 11

[0047] Example 1.1,6-fructose diphosphate inhibits glycolysis of glioma cells

[0048] Human glioma cell lines (U87-MG, U-251, SHG-44) were cultured in medium containing 0.8mM and 1.6mM fructose trisodium salt 1,6-diphosphate and 1.6mM 2-deoxyglucose respectively Culture, 12h, 24h, 36h respectively measure the content of glycolysis end product lactic acid released by the cells in the culture medium. The experimental results showed that the levels of lactic acid in the treatment group were significantly lower than those in the control group without treatment (CON) (***P<0.001 for the comparison between the treatment group and the control group) (Table 1a-c).

[0049] Human glioma cell line (U87-MG) was cultured for 1h, 3h, 6h, 12h, 24h, 36h, 48h in the medium containing 0.8mM 1,6-diphosphate fructose trisodium salt, and analyzed by Western blot. Changes in the levels of key metabolic enzymes in the cellular glycolysis pathway at time points, glucose transporter 1 (GLUT1), hexo...

Embodiment 21

[0059] Example 2. 1,6-Diphosphate fructose trisodium salt promotes mitochondrial oxidative phosphorylation in glioma cells

[0060] Rat glioma cell line (C6), human glioma cell line (KNS-89, SHG-44) were cultured in medium containing 0.8mM or 1.6mM fructose-1,6-diphosphate trisodium salt After 36 hours, the ATP / ADP ratio of each cell line (***P<0.001 compared with the treatment group and the control group) and the NADH / NAD+ ratio were significantly increased (***P<0.001 compared with the treatment group and the control group), and at the same time ATP level was significantly increased (1,6-diphosphate fructose group compared with control group ***P<0.001) (Table 2). The experimental results showed that fructose 1,6-diphosphate promoted mitochondrial oxidative phosphorylation in glioma cells.

[0061] Table 2a. Fructose 1,6-diphosphate increases the ratio of ATP to ADP in glioma cells

[0062]

[0063] Table 2b. Fructose 1,6-diphosphate increases NADH and NAD in glioma cel...

Embodiment 3

[0066] Example 3.1,6-Fructose diphosphate trisodium salt blocks the flow of glycolytic intermediates to biosynthesis

[0067] Human glioma cell line (U87MG) containing 13 C-labeled glucose (U- 13 C-Glc) culture medium and treated with 1.6mM 1,6-diphosphate fructose trisodium salt for 36h, using liquid-mass spectrometry (LC-MS / MS) to measure intracellular glycolysis pathway, pentose phosphate pathway, the "one-carbon unit" metabolic pathway, and intermediates in the de novo nucleic acid synthesis pathway. The experimental results showed: (1) The levels of glycolytic intermediates fructose 1,6-bisphosphate (FBP), glyceraldehyde 3-phosphate (GAP) and phosphoenolpyruvate (PEP) in the treatment group were significantly higher than those in the control group. (Compared with the control group ***P13 Serine (Ser) (M+3) produced by C-Glc through the serine biosynthesis pathway was significantly increased (control group 1±0.03, treatment group 1.57±0.04, ***P13 The proportion of C mar...

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Abstract

The invention provides application of a composition containing fructose-1,6-bisphosphate (FBP) in preparation of antitumor drugs. A proportion of the FBP to metabolic regulators are determined according to respective efficacy doses; the metabolic regulators are different in doses, so that the proportion of the FBP to one metabolic regulator is determined according to the effective dose of the specific metabolic regulator. The composition prevents and cures tumors by damaging activity of a tumor metabolic network. The drugs with the composition as an active ingredient have stronger anticancer efficacy compared with FBP and other metabolic regulators in exclusive use. The composition can completely reverse tumor metabolic characteristics and destroy the tumor metabolic network, prominently featured by blocking glycolysis and an intermediate product of a tricarboxylic acid cycle from biosynthesis while promoting nutriments to enter the tricarboxylic acid cycle and oxidative phosphorylation so as to damage an oxidation-reduction system. The composition is highly safe, and further improves the anticancer efficacy of the FBP.

Description

technical field [0001] The invention belongs to the field of pharmacy and relates to the application of a composition containing fructose-1,6-diphosphate in the preparation of antitumor drugs. Specifically, the composition is composed of fructose-1,6-bisphosphate and other metabolic regulators and / or blood concentration stabilizers of fructose-1,6-bisphosphate, the purpose of which is to destroy the tumor metabolic network, thereby Produces broad-spectrum anticancer activity. Background technique [0002] Cancer has become the first cause of death of human beings, and its morbidity and mortality are still increasing year by year. As early as 1920, German biochemist Otto Warburg proposed the characteristics of tumor cell "aerobic glycolysis", that is, tumor cells still use the enhancement of glycolysis to obtain energy under aerobic conditions, and produce a large number of biosynthetic precursors substance, and proposed that tumor cells are a metabolic disease. However, t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/7024A61K31/353A61K31/155A61K31/122A61K31/717A61P35/00
CPCA61K31/122A61K31/155A61K31/353A61K31/7024A61K31/717A61K45/06A61K2300/00
Inventor 连晓媛张治针胡誉怀毕洪运钱恒
Owner ZHEJIANG UNIV
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