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Application of lithium preparation in preparation of anti-osteosarcoma medicament

A technology for osteosarcoma and preparations, which is applied in the application field of preparing targeted therapy drugs for osteosarcoma, and can solve the problems such as no reports on the application of lithium salt targeted anti-osteosarcoma therapy.

Inactive Publication Date: 2011-03-30
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, lithium has been widely used in psychiatric clinics by the world psychiatric community, but so far, there are no reports on the application of lithium salts in targeted anti-osteosarcoma therapy

Method used

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  • Application of lithium preparation in preparation of anti-osteosarcoma medicament
  • Application of lithium preparation in preparation of anti-osteosarcoma medicament
  • Application of lithium preparation in preparation of anti-osteosarcoma medicament

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] [Example 1] Function of GSK-3β in osteosarcoma cell lines.

[0018] 1.1 Test material

[0019] 1.1.1 Cell lines: U2OS, U2OS / MTX300, MG63, SAOS2, ZOS, ZOS-M

[0020] 1.1.2 Experimental animals: 6-8 weeks old BALB / c nude mice (purchased from Guangdong Experimental Animal Center)

[0021] 1.1.3 Reagents: Thiazolium blue (MTT) (Sigma, the production company in brackets, the same below), propidium iodide (PI) (Sigma), DMSO dimethyl sulfoxide (Sigma), LiCl (Sigma), DMEM (a medium containing various amino acids and glucose) culture medium (Gibico), fetal bovine serum (Hangzhou Sijiqing Biological Co., Ltd.), anti-GSK-3β (primary antibody, Cell signal), anti-P-GSK- 3β-9Ser (primary antibody, Cell signal), anti-Caspase3 (primary antibody, Santa Cruz), anti-bc12 (primary antibody, Santa Cruz), anti-bax (primary antibody, Santa Cruz), lipofectamine 2000 (Invitrogen), small Fragment interference ribonucleic acid GSK-3β (siRNA-GSK-3β, Guangzhou Ruibo Synthetic), pcDNA3.1, GSK-3β-...

Embodiment 2

[0062] [Example 2] Anti-osteosarcoma mechanism in LiCl cells

[0063] 2.1 Experimental materials

[0064] 2.1.1 Cell lines: cell lines VEC1, VEC2, CA3, CA9, KD2, KD5 stably transfected with GSK-3β

[0065] 2.1.2 Reagent: Apoptosis-related protein chip (R&D)

[0066] 2.2 Experimental method

[0067] 2.2. After the osteosarcoma cells were treated with 120mM LiCl for 72 hours, the flow cytometric detection method was the same as above.

[0068]2.2.2 Detection of protein chip: After treating osteosarcoma cells with 20mM LiCl for 72 hours, the protein cleavage method was the same as that of western blot. The rest of the experimental steps were operated according to the method in the R&D protein chip kit. Use flat-tip tweezers to take the chip out of the plastic protective film, place it in the four-well plate in the kit, with the numbered side facing up, and add 2ml of buffer 1 to it for blocking. Incubate on a shaker at room temperature for 1 h. In a separate tube, add the a...

Embodiment 3

[0085] [Example 3] Involved mechanism of LiCl intracellular anti-osteosarcoma.

[0086] 3.1 Experimental materials

[0087] 3.1.1 Cell line: human osteosarcoma cell line ZOS

[0088] 3.1.2 Experimental animals: BALB / c nude mice aged 6-8 weeks, purchased from Guangdong Experimental Animal Center.

[0089] 3.2 Experimental method: Nude mice were randomly divided into control group (normal saline), doxorubicin group (6mg / kg), lithium chloride group (340mg / kg), lithium chloride (340mg / kg) + small dose of adriamycin Mycin group (3mg / kg), lithium chloride (340mg / kg) + high-dose doxorubicin group (6mg / kg), 6 rats in each group. Inoculate 5×10 subcutaneously in the right armpit 6 Cells were confirmed to be tumor-forming and mung bean-sized tumors were palpable when the administration was started (generally, the administration was started on the tenth day after inoculation). LiCl was administered intraperitoneally once every other day, and Adriamycin was administered intraperitonea...

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Abstract

The invention relates to new application of a lithium preparation in targeted therapy of osteosarcoma, and belongs to the technical field of medicaments. Shown by experiments, the lithium preparation has remarkable in vivo and in vitro anti-osteosarcoma effects; the effects of the lithium preparation are possibly realized by phosphorylating GSK-3beta (glycogen synthase kinase 3beta) to inhibit the function of the lithium preparation; and when the lithium preparation is used with classical chemotherapeutic adriamycin medicament and the like, the tumor killing effect of the lithium preparation is obviously enhanced. The lithium salt in the lithium preparation is selected from lithium chloride, lithium carbonate, lithium sulfate, lithium citrate, lithium orotate or other pharmaceutical or used lithium salt. The medicament can be orally taken or injected and also can be compounded with other medicaments such as adriamycin to form a compound preparation and when the preparation is prepared, the preparation contains the lithium salt and pharmaceutically acceptable carrier or excipient.

Description

technical field [0001] The present invention mainly relates to the application of lithium salt in the preparation of drugs for targeted treatment of osteosarcoma. Background technique [0002] Glycogen synthase kinase 3β (Glycogen Synthase Kinase 3β, GSK-3β) is a protein molecule with the function of serine / threonine kinase, which is involved in the regulation of transcription, glucose metabolism, cell cycle, apoptosis, stem cell development, etc. A series of important functions within. In terms of disease occurrence, its inhibition of glycogen synthesis is considered to be an important mechanism of non-insulin diabetes; it promotes the occurrence of certain inflammations through the activation of intracellular NF-KB; the hyperphosphorylation of tau protein makes it in Play an important pathogenic role in Alzheimer's disease and other degenerative disorders of the nervous system. In tumor cells, GSK-3β also participates in the regulation of Wnt, Hedgehog and other pathways...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/00A61K31/513A61K31/704A61P35/00
Inventor 沈靖南康铁邦王晋谢显彪唐清连尹军强邹昌业曾益新
Owner SUN YAT SEN UNIV
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