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Application of oridonin in preparing activator of tumor-suppressor protein FBW7

A technology of Rubescensine A and tumor suppressor protein, which is applied in the fields of medicine, biochemistry and cell biology, can solve problems such as no discovery, and achieve the effects of low human toxicity, easy preparation and strong applicability

Inactive Publication Date: 2012-07-04
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, no drugs and technical means to activate FBW7 have been found

Method used

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  • Application of oridonin in preparing activator of tumor-suppressor protein FBW7
  • Application of oridonin in preparing activator of tumor-suppressor protein FBW7
  • Application of oridonin in preparing activator of tumor-suppressor protein FBW7

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1 Rubescensine A activates FBW7 protein in K562 cells and promotes ubiquitin-proteasome degradation of its substrate protein

[0026] K562 cells were divided into 3×10 5 / mL density was inoculated in 24-well plates, and Rubescensin A was added the next day to make the final concentration 20 μmol / L. Subsequently, the cells were collected at 0, 2, 4, 6, 8, 10, and 12 hours, and the proteins were lysed and detected by immunoblotting for FBW7 and its substrate proteins: c-Myc, CyclinE (cyclin E), mTOR (mammalian Expression of animal target of rapamycin). See the experimental results figure 1 , the protein levels of the three isoforms of FBW7 gradually increased over time under the induction of Rubescensin A, while the housekeeping gene GAPDH (glyceraldehyde-3-phosphate dehydrogenase) as an internal control did not change. Oridonin can not only activate FBW7 in a short period of time, but also the effect will be more significant as the induction time prolongs. At...

Embodiment 2

[0028] Example 2 Oridonin A promotes the binding of FBW7 to its substrate protein

[0029] We induced K562 cells with 20 μmol / L oridonin, collected the cells and lysed the protein after 2 hours. Cell lysates were co-immunoprecipitated using c-Myc-specific antibodies, and the precipitated protein complexes were immunoblotted to detect FBW7 in the protein complexes. from image 3 It can be seen from the results that Rubescensin A significantly increased FBW7 in the c-Myc immunoprecipitated protein complex, that is, Rubescensin A significantly enhanced the binding ability of FBW7 to the substrate protein c-Myc .

Embodiment 3

[0030] Example 3 The growth inhibition and apoptosis induction effect of oridonin on K562 cells

[0031] We divided K562 cells into 3 × 10 5 The cells were inoculated in 96-well plates at a density of / mL, and treated with 5-80 μmol / L oridonin for 24 hours the next day (with DMSO as the control), and then the cell viability was detected by MTT. See the experimental results Figure 4 A, The cell viability was not significantly affected by the low concentration of Rubescensin A treatment, and the concentration above 20 μmol / L could significantly reduce the survival rate of K562 cells. The inhibitory effect of oridonin on K562 cells was positively correlated with drug dosage.

[0032] K562 cells were induced with 20 μmol / L oridonin for 24 hours (DMSO was used as the control), the collected cells were washed once with PBS, and stained with DAPI for 5 minutes. Examined under a fluorescent microscope, most of the cells undergo apoptosis, which can be deeply stained by DAPI, and n...

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PUM

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Abstract

The invention discloses an application of oridonin in preparing an activator of tumor-suppressor protein FBW7 (F-box and WD repeat domain containing 7). According to a large number of studies, oridonin can activate the expression of FBW7 protein and enhance the affinity of FBW7 protein to a substrate protein, so that FBW7-medicated ubiquitination degradation pathway is rapidly and efficiently activated. Oridonin target-degrades cancer protein such as c-Myc, cyclinE and mTOR through activation of the FBW7-medicated ubiquitination degradation pathway, so as to inhibit the growth of a variety oftumor cells and induce cell apoptosis. Oridonin is mainly derived from traditional Chinese medical material Rabdosia rubescens, is easy to prepared, has low toxicity to human body, and has high applicability.

Description

technical field [0001] The invention belongs to the technical fields of medicine, biochemistry and cell biology, and specifically relates to the use of oridonin in the preparation and activation of the tumor suppressor protein FBW7 and the targeted ubiquitination degradation of oncoproteins c-Myc, cyclin E and Anti-tumor drugs such as mTOR; and as a cell inducer for activating FBW7 and interfering with the expression of its substrate proteins (including c-Myc, cyclin E and mTOR, etc.) in basic research, providing methods and methods for studying the biological functions of the above proteins means. Background technique [0002] Tumors, especially malignant tumors, are a major disease that threatens human health. Tumor treatment is a major medical problem facing mankind today. With the continuous development of science, professionals have conducted in-depth research on the causes of tumors, and the mechanism of gene carcinogenesis has gradually become clear. The technology ...

Claims

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Application Information

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IPC IPC(8): A61K31/352A61P35/00A61P35/02
Inventor 黄慧琳翁桁游周惠屈良鹄
Owner SUN YAT SEN UNIV
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