Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of carbon-21 steroid compound STA in preparation of Hedgehog pathway inhibitor and anticancer drugs

A technology of steroid compounds and anticancer drugs, applied in the field of medicine

Active Publication Date: 2015-10-07
ZHEJIANG ACAD OF MEDICAL SCI
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Since its chemical structure was reported, only studies on the anti-inflammatory and immunosuppressive activities of this compound have been reported (Chen F, Ni Y, Ye Y, et al. Stephanthraniline A inhibits the proliferation and activation of T cells in vitro and in vivo. Eur J Pharmacol,2012,15,685(1-3):186-97), there is no report about its inhibition of Hedgehog pathway and induction of tumor cell apoptosis and its application in anticancer drugs

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of carbon-21 steroid compound STA in preparation of Hedgehog pathway inhibitor and anticancer drugs
  • Application of carbon-21 steroid compound STA in preparation of Hedgehog pathway inhibitor and anticancer drugs
  • Application of carbon-21 steroid compound STA in preparation of Hedgehog pathway inhibitor and anticancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Inhibitory effect of STA on tumor cell proliferation

[0038] 1.1 Experimental method

[0039] 1.1.1 Cell culture

[0040] Human gastric cancer SGC-7901 cells, human liver cancer Hep G2 cells, human non-small cell lung cancer A549 cells, human lung adenocarcinoma HCC-827 cells, human pancreatic cancer cells PANC-1 cells, human prostate cancer DU145 cells, human ovarian cancer COC1 cells And human breast cancer MDA-MB-231 cells were cultured in DMEM medium containing 10% inactivated fetal bovine serum, 100IU / mL penicillin, 100μg / mL streptomycin; human colon cancer cell HT-29 cells were cultured in 10 % inactivated fetal bovine serum, 100IU / mL penicillin, 100μg / mL streptomycin in McCoy's 5A medium; place at 37°C, 5% CO 2 cultured in a cell culture incubator. When the cells grew more than 80% confluent, they were digested and passaged with 0.25% trypsin.

[0041] 1.1.2 Determination of the inhibitory effect of STA on tumor cell proliferation

[0042] Take t...

Embodiment 2

[0045] Example 2: Inhibitory effect of STA on Hedgehog pathway

[0046] 2.1 Experimental method

[0047] 2.1.1 Cell culture

[0048] Shh-LightⅡ cells were cultured in DMEM medium containing 10% inactivated fetal bovine serum, 400 μg / ml G418 and 0.15 mg / ml Zeocin; Shh-N overexpression 293 cells were cultured in DMEM medium containing 10% inactivated fetal bovine serum, 400 μg / ml ml G418 in DMEM medium; place at 37°C, 5% CO 2 cultured in a cell culture incubator. When the cells grew more than 80% confluent, they were digested and passaged with 0.25% trypsin.

[0049] 2.1.2 Preparation of SCM (Shh-conditioned Medium)

[0050] After the Shh-N overexpression 293 cells were about 80% confluent, they were replaced with a medium containing 2% fetal bovine serum and cultured for 24 hours. The supernatant was taken and filtered through a 0.22 μm membrane to obtain the SCM solution.

[0051] 2.1.3 Determination of the inhibitory effect of STA on the Hedgehog pathway

[0052] Take S...

Embodiment 3

[0055] Example 3: Inhibitory effect of STA on Hedgehog pathway-related genes in human colon cancer cell line HT-29

[0056] 3.1 Experimental method

[0057] Take HT-29 cells in the logarithmic growth phase and adjust the concentration to 1×10 5 cells / mL, seeded in 24-well cell culture plate, 1 mL / well. After culturing for 24 hours, add STA diluent to a total volume of 2 mL / well, and set solvent control wells, each with 3 wells. After continuing to culture for 24 hours, the cells were collected to extract RNA, and the mRNA expression of genes related to Hedgehog pathway was analyzed by fluorescent real-time quantitative PCR. The results were as follows: image 3 shown.

[0058] 2.2 Experimental results

[0059] from image 3 It can be seen that STA at 50 μM can significantly inhibit the mRNA expression of Gli1, Gli2, Gli3, Ptch and Sufu genes in HT-29 cells, indicating that STA inhibits the proliferation of HT-29 cells and its inhibition of the Hedgehog pathway is related....

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides application of a carbon-21 steroid compound STA in preparation of a Hedgehog pathway inhibitor and anticancer drugs. The structural formula of the carbon-21 steroid compound STA is described in the specification. The compound can be applied to preparation of drugs used for treating cancers including, but not limited to, basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, pancreatic cancer, breast cancer, spinal meningioma, malignant glioma, melanoma, stomach cancer, liver cancer, esophageal cancer, bile duct cancer, prostatic cancer, colorectal cancer, small cell lung cancer, non-small cell lung cancer, neurogliocyte cancer, multiple myeloma, urogenital neoplasms and leukemia. Experiment results prove that the compound is capable of both inhibiting the Hedgehog pathway and inducing apoptosis of tumor cells.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of a natural or synthetic carbon-21 steroid compound Stephanthraniline A (STA) in the preparation of Hedgehog pathway inhibitors and anticancer drugs. Background technique [0002] The Hedgehog (Hh) signaling pathway is mainly composed of the extracellular Hh protein, the specific transmembrane receptor Patched (Ptch) on the surface of the cell membrane, the migration transmembrane protein Smoothened (Smo) and the intracellular transcription factor Gli. Hh is a highly conserved secreted protein. In mammals, the Hh gene encodes three proteins: Shh (Sonic hedgehog), Ihh (Indian hedgehog) and Dhh (Desert hedgehog). Hh signals are transmitted intracellularly through Ptch receptors and Smo. In the absence of Hh protein, Ptch inhibits Smo. When Hh protein binds to Ptch, the inhibitory effect on Smo is released, and the activated Smo starts the cascade reaction of intr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/565A61P35/00A61P35/02
Inventor 陈峰阳叶益萍李晓誉王一奇徐世芳高丽娟
Owner ZHEJIANG ACAD OF MEDICAL SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com