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Antitumor drug composition as well as application of reagent comprising iron ions

A technology of iron ions and compositions, applied in the field of iron ions and/or ROS inducers in the preparation of drugs for the treatment of tumors, which can solve the problems of high mortality, broad-spectrum limitations, and unsatisfactory therapeutic effects

Inactive Publication Date: 2018-11-02
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to relevant research data in the United States, the clinical anti-cancer effect brought by PD-1 is remarkable. It can control the disease progression of 50% of malignant melanoma patients, but its broad-spectrum is limited.
Although some progress has been made in the treatment of malignant melanoma, due to its high mortality rate, the newly developed drugs still have problems such as not having a broad therapeutic range and unsatisfactory therapeutic effect. , more efficient, and specific drug candidates for the treatment of melanoma are particularly important

Method used

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  • Antitumor drug composition as well as application of reagent comprising iron ions
  • Antitumor drug composition as well as application of reagent comprising iron ions
  • Antitumor drug composition as well as application of reagent comprising iron ions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] FeSO 4 Effects of the combination with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the induction of pyroptosis in human malignant melanoma cell line A375.

[0078] experimental method:

[0079] Analysis of pharmaceutical composition FeSO by microscopic photographing technique 4 Effect of the combination with Carbonylcyanide 3-chlorophenylhydrazone (CCCP) on pyroptosis induction of human malignant melanoma cell line A375.

[0080] The experimental method is as follows:

[0081] 1. Take various cancer cell lines in the logarithmic growth phase, and use 4×10 5The cells / mL density were seeded on 6-well culture plates;

[0082] 2. After culturing overnight, replace the culture medium with DMEM containing 0.5% serum, and use DMSO, CCCP (20 μM, dissolved in DMSO), FeSO 4 (100μM, dissolved in H 2 O), CCCP (20μM) and FeSO 4 (100 μM) the composition to treat the cells;

[0083] After 3.24 hours, observe the cell morphology with a microscope and take pictures. Phot...

Embodiment 2

[0088] Pharmaceutical composition FeSO of the present invention 4 Effects of the combination with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the induction of pyroptosis in human malignant melanoma cell line A375.

[0089] experimental method:

[0090] Adopt immunoblotting analysis (Western blotting) method to analyze composition FeSO of the present invention 4 Effects of the combination with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the induction of pyroptosis in human malignant melanoma cell line A375.

[0091] The experimental method is as follows:

[0092] 1. Take various cancer cell lines in the logarithmic growth phase, and use 4×10 5 The cells / mL density were seeded on 6-well culture plates;

[0093] 2. After culturing overnight, replace the culture medium with DMEM containing 0.5% serum, and use DMSO, CCCP (20 μM, dissolved in DMSO), FeSO 4 (100μM, dissolved in H 2 O), CCCP (20μM) and FeSO 4 (100 μM) the composition to treat the cells;

[0094] ...

Embodiment 3

[0111] Pharmaceutical composition FeSO of the present invention 4 The effect of the combination with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the growth of human malignant melanoma cell line A375.

[0112] experimental method:

[0113] Adopt promega company's cytotoxicity detection kit to detect the release of lactate dehydrogenase and analyze the pharmaceutical composition FeSO of the present invention 4 The effect of the combination with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the growth of human malignant melanoma cell line A375.

[0114] The experimental method is as follows:

[0115] 1. Take various cancer cell lines in the logarithmic growth phase, and use 4×10 5 The cells / mL density were seeded on 6-well culture plates;

[0116] 2. After culturing overnight, replace the culture medium with DMEM containing 0.5% serum, and use DMSO, CCCP (20 μM, dissolved in DMSO), FeSO 4 (100μM, dissolved in H 2 O), CCCP (20μM) and FeSO 4 (100 μM) the composit...

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Abstract

The invention relates to a reagent (ii) ROS inducing agent comprising (i) iron ions or a drug composition of a combination of a pharmaceutically-acceptable salt thereof and application in treating tumors. The drug composition can cause the pyroptosis of tumor cells, can inhibit the growth and transfer of the tumor, and can be used as a candidate drug for treating the tumor.

Description

technical field [0001] The invention relates to an antitumor pharmaceutical composition, a method for treating tumors, and the use of iron ions and / or ROS inducers in preparing medicines for treating tumors. Background technique [0002] Ferroptosis was newly proposed by Dixo et al. [Dixon S J, Lemberg K M, Lamprecht MR, et al. Ferroptosis: aniron-dependent form of nonapoptotic cell death. Cell, 2012,149(5):1060-1072] A mode of cell death caused by iron-dependent oxidative damage that is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. Typical features of apoptosis include cell shrinkage, nuclear condensation, chromatin fringe collection, DNA degradation, membrane blebbing, nuclear and cytoplasmic fragmentation into apoptotic bodies, which are engulfed and degraded by neighboring cells. The morphological features of necrosis are swelling of cells and organelles, rupture of membranes, dissolution of nuclear chromosomes rather ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K33/26A61K31/655A61P35/00
CPCA61K31/655A61K33/26A61K45/06A61P35/00A61K2300/00
Inventor 吴乔周波张嘉媛陈航姿
Owner XIAMEN UNIV
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