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Application of ailanthone to preparation of medicines for treating prostatic disease

A technology of Ailanthus ketone and prostate, applied in the field of medicine

Active Publication Date: 2015-11-25
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The latest FDA-approved drugs for the treatment of castration-resistant prostate cancer (CastrationResistantProstateCancer, CRPC) include Abiraterone (Abiraterone) and MDV3100 (Enzalutamide), the former inhibits the synthesis of androgen, and the latter is an antagonist of the androgen receptor. These two drugs are aimed at the androgen receptor signaling pathway, and have achieved a certain effect in the treatment of castration-resistant prostate cancer (CRPC). However, after the above drug treatment, the patient will still develop drug resistance, and the above two drugs This kind of medicine is not a medicine with independent intellectual property rights in my country

Method used

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  • Application of ailanthone to preparation of medicines for treating prostatic disease
  • Application of ailanthone to preparation of medicines for treating prostatic disease
  • Application of ailanthone to preparation of medicines for treating prostatic disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Embodiment 1: Formula (I) Ailanthione inhibits the transcriptional activity of androgen receptor in vitro

[0079] Technical method:

[0080] 1. Cell Culture

[0081] The cells used in this experiment were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences. Some cells came from the laboratory of Professor Weng Jiemin, Shanghai Key Laboratory of Regulatory Biology; another cell line came from the Changhai Hospital affiliated to the Second Military Medical University. The isolated prostate cancer cells were cultured in a constant temperature incubator at 37°C (humidity 95%, CO 2 concentration 5%), the medium was RPMI-1640 (6ibco) containing 10% fetal bovine serum (Front).

[0082] 2. Dual luciferase reporter gene detection

[0083] The plasmids used in this experiment are MMTV-LUC (nuclear hormone receptor reporter gene) and Renila (internal control reporter gene). MMTV-LUC is a reporter gene plasmid with androgen receptor transcription activatio...

Embodiment 2

[0085] Embodiment 2: formula (I) Ailanthus ketone inhibits the proliferative activity and clone formation of different prostate cancer cells

[0086] Technical method:

[0087] 1. SRB (sulfonyl rhodamine) assay for cell proliferation

[0088] Different prostate cell lines in 5×10 3 Cells / well were inoculated into 96-well plates (Corning). After 24 hours, different concentrations of the monomeric compound were added, and the same amount of DMSO was added to the control group. Six replicate wells were set up in each group. After continuing to culture for 24h, 48h and 72h respectively, add pre-cooled TCA (trichloroacetic acid, 50%, w / V) and incubate at 4°C for more than 60min to fix the cells. After fixing, rinse with running water 5 times and air dry. Add 50 μl of SRB staining solution (4%, w / V) to each well and incubate at room temperature for 10 minutes for staining. Aspirate the dye solution, add 100 μl of 1% acetic acid to each well and wash 5 times to remove unbound dye...

Embodiment 3

[0097] Embodiment 3: the inhibitory effect of formula (I) ailanthione monomer on the migration ability of prostate cancer cells

[0098] Technical method:

[0099] 1. Streak Migration Experiment

[0100] In order to study whether formula (I) Ailanthus ketone inhibits the lateral migration of cells, cells are inoculated to 6-well plates, and tumor cells are incubated at 37° C. in 5% CO 2 Routine culture in the incubator for 24 hours until the cells grow to 100% full. The serum-free medium was replaced, and the culture was continued for 12 h. In the culture wells full of cells, scratch with a 200 μl sterilized tip (tip), wash the cells twice with PBS after scratching, wash away the floating cells, and add 1 ml of complete medium to each well. Add different concentrations of drugs to the cell culture wells respectively, and place the culture plate in CO 2 Incubator, 37 ℃ for 24 hours to continue routine cultivation. Observe the movement of the cells to the lined part under a...

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Abstract

The invention provides application of ailanthone (AIL) which is shown in a formula (I) and is a monomer of Chinese traditional herbs to preparation of medicines for treating prostatic disease. By a compound, in-vitro and / or in-vivo growth and migration of prostate carcinoma cells can be suppressed obviously, protein expression level of an androgen receptor in the prostate carcinoma cells is reduced, and a signal path of the androgen receptor is suppressed. The compound has a prostate cancer treatment application prospect.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of ailanthione, a monomer of traditional Chinese medicine, in the preparation of medicaments for treating prostate diseases. Background technique [0002] Prostate cancer (PCa) is the most common malignant tumor of the male reproductive system, and its incidence increases with age. In my country, the incidence rate of prostate cancer increased from 1.71 per 100,000 male population in 1993 to 7.9 per 100,000 male population in 2005. The rate (world standard rate) is 6.73 / 100,000. The incidence of prostate cancer in my country shows an obvious and continuous growth trend, and prostate cancer is becoming a malignant tumor of the urinary system that seriously affects the health of men in my country (Analysis of the incidence status and epidemic trend of prostate cancer in China, "Journal of Clinical Oncology" 2013 Issue 04). [0003] Prostate cancer has a long incub...

Claims

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Application Information

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IPC IPC(8): A61K31/366A61P35/00
Inventor 易正芳何云东王金花彭世鸿刘明耀
Owner EAST CHINA NORMAL UNIVERSITY
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