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A kind of application of betaine

A technology of betaine and bortezomib, which is applied in the field of biomedicine, can solve problems such as refractory effects, drug resistance, and recurrence, and achieve the effects of reducing side effects, improving treatment plans, and inhibiting cell proliferation

Active Publication Date: 2022-05-10
CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, the important clinical problems are drug resistance and recurrence. The reason why the existing MM treatment drugs and regimens ultimately fail is because the occurrence and development of MM and the mechanism of drug resistance of recurrence are extremely complex, involving tumor initiating cells (stem / progenitor cells) and clonal evolution , Abnormalities of various signaling pathways caused by genetic changes, vicious circle interaction between tumor cells and bone marrow microenvironment and other multi-faceted and multi-dimensional mechanisms. To improve the therapeutic effect, it is necessary to take tumor drug-resistant cells and their bone marrow microenvironment as a whole, and conduct in-depth research on the complex mechanism of interaction between MM cells and microenvironment at the cellular and molecular levels, in order to elucidate the new mechanism of MM drug resistance and The development of biomarkers for clinical early warning provides a new idea

Method used

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  • A kind of application of betaine
  • A kind of application of betaine
  • A kind of application of betaine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Detection of glycine content in healthy controls and multiple myeloma patients

[0032] In the embodiment, bone marrow supernatant and serum samples from 31 healthy donors (HD) and 111 patients with newly diagnosed multiple myeloma, as well as CD138 + Plasma cells and CD138 in 16 newly diagnosed multiple myeloma patients + Tumor cell samples, all samples came from Xiangya Hospital Affiliated to Central South University, Second Xiangya Hospital Affiliated to Central South University, Third Xiangya Hospital Affiliated to Central South University, and Tianjin Hospital of Blood Diseases, Chinese Academy of Medical Sciences. All patients with multiple myeloma were diagnosed as patients with multiple myeloma by detecting the type of serum monoclonal immunoglobulin and the proportion of plasma cells in bone marrow, and all of them were newly diagnosed patients without treatment to exclude metabolic changes caused by treatment. Healthy donors were age, sex, and body...

Embodiment 2

[0038] Example 2: Effects of Glycine Analogues on the Proliferation of Multiple Myeloma Cells

[0039]Currently there are 2 known glycine analogues, including N,N-dimethylglycine (DMG) and betaine (Betaine), both of which are natural compounds and are intermediate metabolites of glycine produced by the decomposition of choline.

[0040] Purchase betaine (CAS: 107-43-7, Sigma) and DMG (CAS: 1118-68-9, Sigma) powders respectively, weigh an appropriate amount of powders according to the product instruction manual, prepare 100mg / ml mother liquor, and store at -80°C until use.

[0041] The human multiple myeloma cell ARP1 (purchased from The Global Bioresource Center, ATCC) and the murine multiple myeloma cell line 5TGM1 (gifted by Zheng Yuhuan's research group of Sichuan University) were selected for phenotypic analysis. The above two cell lines All were identified as correct cell lines by cell STR typing test. The above two cell densities were adjusted to 5000 cells / 100 μl, mix...

Embodiment 3

[0043] Example 3: Effects of Betaine on Intracellular Glycine Content

[0044] In order to confirm that betaine can effectively inhibit the uptake of exogenous glycine by multiple myeloma, high performance liquid chromatography (High Performance Liquid Chromatography, HPLC) was used to detect the content of glycine in the cells of multiple myeloma cells treated with betaine.

[0045] Human multiple myeloma cell ARP1 and murine multiple myeloma cell line 5TGM1 were selected for detection. in 5x10 6 Add / do not add 2mg / ml betaine to each cell, collect the same number of cells after 48 hours, centrifuge to collect the precipitate, and then perform sample pretreatment. Freeze and thaw twice, then add 20 μl 5% salicylic acid, ice bath for 10 minutes, centrifuge at 8000 rpm for 5 minutes, take the supernatant to be tested, and store it temporarily at -80°C.

[0046] The reagents and instrument conditions required for HPLC are as follows:

[0047] Mobile phase: A: 50mM sodium aceta...

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Abstract

The invention discloses an application of betaine for the first time. Betaine is an alkaloid widely present in animals and plants. Its chemical name is N,N,N-trimethylglycine. Its chemical structure is similar to that of glycine. It is a quaternary ammonium base with a molecular formula of C 5 h 11 NO 2 . The present invention finds for the first time that betaine can be used alone or in combination with bortezomib for the treatment of multiple myeloma (Multiple Myeloma, MM). The invention discloses the therapeutic effect of betaine on multiple myeloma, has inhibitory effect on the progress of multiple myeloma, and has great significance for the basic research and clinical treatment of multiple myeloma.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the use of betaine in preparing medicines for treating multiple myeloma and the mechanism of betaine for treating multiple myeloma. Background technique [0002] Multiple myeloma (MM) is a malignant tumor of the blood system, mainly characterized by abnormal proliferation of bone marrow plasma cells and excessive production of monoclonal immunoglobulin or light chain (M protein). Its incidence rate is about 2 to 3 people / 100,000 people, and it is more common in the elderly over 60 years old; with the aging population in my country in recent years, the number of MM cases is on the rise. Clinically, MM patients are often accompanied by multiple osteolytic lesions, hypercalcemia, anemia, and kidney damage; and due to the inhibition of normal immunoglobulin production, MM patients are susceptible to various bacterial infections. [0003] At present, the important clinical problems are dru...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/205A61K31/69A61K38/05A61P35/00
CPCA61K31/205A61K31/69A61K38/05A61P35/00A61K2300/00
Inventor 周文张靖宇贾伟夏机良
Owner CENT SOUTH UNIV
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