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Pharmaceutical use of triptolide

A technology of triptolide and tripterygium, which is applied in the field of preparation of anti-hematological malignancy drugs, can solve the problems of unseen research reports, hormone resistance and sensitivity reduction, etc.

Inactive Publication Date: 2009-07-22
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Drug resistance and reduced sensitivity to hormones are also the main reasons for limiting its application
However, there is no research report on the mechanism of triptolide's resistance to dexamethasone

Method used

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  • Pharmaceutical use of triptolide
  • Pharmaceutical use of triptolide
  • Pharmaceutical use of triptolide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Embodiment 1 Steps and methods of mechanism discovery

[0016] We studied the effect of IL-6 on TPL-induced dexamethasone-sensitive and drug-resistant multiple myeloma cell lines MM.1S, MM.1R. The results of MTT colorimetric assay showed that 50ng / ml IL-6 could promote the growth of MM.1S and MM.1R cells, and the cell survival rates were 123±3.64% and 109±5.77%, respectively. 5ng / ml TPL treated MM.1 cells for 24h alone and in combination with IL-6 (50ng / ml), IL-6 could not antagonize TPL-induced growth inhibition of MM.1 cells, the cell survival rate was 42.33±2.36%, 64 ±3.17%, 61±2.08% and 72.33±3.98% when combined with IL-6. There were significant differences among the groups (Pfigure 1 . In the figure a is the dexamethasone-sensitive multiple myeloma cell line MM.1S, b is the dexamethasone-resistant multiple myeloma cell line MM.1R, 1 is the control, and 2 is the interleukin 650ng / ml treatment group , 3 is the triptolide 10ng / ml dose treatment group, 4 is the comb...

Embodiment 2

[0046] Effect of IL-6 on TPL-induced dexamethasone-sensitive and drug-resistant multiple myeloma cell lines MM.1S, MM.1R.

[0047] We studied the effect of IL-6 on TPL-induced dexamethasone-sensitive and drug-resistant multiple myeloma cell lines MM.1S, MM.1R. The results of MTT colorimetric assay showed that 50ng / ml IL-6 could promote the growth of MM.1S and MM.1R cells, and the cell survival rates were 123±3.64% and 109±5.77%, respectively. 5ng / ml TPL treated MM.1 cells for 24h alone and in combination with IL-6 (50ng / ml), IL-6 could not antagonize TPL-induced growth inhibition of MM.1 cells, the cell survival rate was 42.33±2.36%, 64 ±3.17%, 61±2.08% and 72.33±3.98% when combined with IL-6. There were significant differences among the groups (Pfigure 1 (Same diagram as above).

[0048] MTT detection MTT colorimetric method to detect cell proliferation:

[0049] Take cells in logarithmic growth phase, wash with fresh culture medium, resuspend in RPMI1640 culture medium co...

Embodiment 3

[0051] We applied real-time quantitative PCR method, common PCR method, and Western-blot method to detect the expression of GR in MM.1 cells treated with TPL. The results showed that 5-20ng / ml TPL treatment of MM.1 cells caused GR to The expression level and protein level increase, and the characteristics of the increase are also positively correlated with the apoptosis events mediated by the caspase family. For the relative expression of the target protein, see image 3 .

[0052] figure 2 The results showed that 5-20ng / mlTPL treatment of MM.1 cells caused an increase in the expression of GR at the mRNA level and protein level. figure 2 A is Real-time PCR method detection, figure 2 B is the result detected by common PCR method, figure 2 C is the increase in the expression of hormone receptors at the protein level detected by Western-blot method. In the figure, 0, 5, 10, and 20 are the treatment concentrations of triptolide, and the unit is ng / ml, * indicates that the ...

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Abstract

The invention provides application of triptolide in preparation of a medicine for reversing the drug resistance of dexamethasone, in particular application of the triptolide in a medicine for reversing the drug resistance of the dexamethasone in multiple myeloma. The research proves that the triptolide has the characteristic of reversing the drug resistance of the multiple myeloma to the dexamethasone, and the characteristic cannot be antagonized by interleukin-6. The invention lays an experimental basis for the triptolide to prepare a novel medicine which is ideal, reverses the drug resistance, and resists malignant tumor of a blood system. The utilization of a mechanism that the triptolide reverses the drug resistance can provide the triptolide with a theoretical evidence for treating diseases with the drug resistance to hormone, open a new field for the treatment of drug resistance recurrence of malignant blood tumor patients, and create novel medicines for target therapy of the drug resistance.

Description

technical field [0001] The invention belongs to the use of medicine, and relates to a new mechanism of reversing drug resistance of triptolide and its application in the preparation of anti-hematological malignancy drugs. Background technique [0002] Triptolide (triptolide; also known as triptolide, PG-490), is a diterpene lactone compound containing 3 epoxy groups isolated from Tripterygium wilfordii. The appearance is colorless needle-like crystals, the relative molecular mass is 360, and the molecular formula is C 2 Oh 24 o 6 , chemically stable in vivo. Physiologically active, it is one of the main components of Tripterygium wilfordii to exert immunosuppressive effect and anti-tumor formation, its related potency is 100-200 times higher than that of tripterygium glycosides, and it has the characteristics of broad anti-tumor spectrum and strongest anti-tumor property . Compared with other monomers of Tripterygium wilfordii, triptolide is easier to obtain, and the to...

Claims

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Application Information

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IPC IPC(8): A61K31/585A61P35/00A61P35/02C07J73/00
Inventor 金洁杨敏
Owner ZHEJIANG UNIV
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