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Application of artemisinin in drugs to kill breast carcinoma stem cells

A technology of human breast cancer cells and stem cells, which is applied in the application field of cancer treatment drugs, can solve the problems of tumor stem cells not producing a good killing effect, tumor recurrence, tumor resistance and other problems, so as to improve the quality of life, improve the tumor curative effect, The effect of prolonging the survival time

Active Publication Date: 2019-06-21
JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Even if the vast majority of tumor cells are killed, as long as there are surviving tumor stem cells, it will still cause tumor recurrence and metastasis
At present, most of the clinical anti-tumor treatments can not produce a good killing effect on tumor stem cells, and enrich the tumor stem cells to a certain extent, which in turn leads to drug resistance and recurrence of tumors.

Method used

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  • Application of artemisinin in drugs to kill breast carcinoma stem cells
  • Application of artemisinin in drugs to kill breast carcinoma stem cells
  • Application of artemisinin in drugs to kill breast carcinoma stem cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 Tumor stem cell induction and sphere formation experiment

[0054] Through this example, the induction and cultivation of several tumor stem cells are constructed to provide research objects for the follow-up.

[0055] HepG2, MNNG / HOS, SKOV-3, BT474, A549, MCF-7, BGC-823, MDA-MB-231, T47D cells at 500 cells / cm 2 The density was inoculated in 1.2% poly(2-hydroxyethyl methacrylate) and 95% ethanol-coated plates (Sigma-Aldrich), and cultured in the absence of DMEM / Ham nutrient mixture F-12 (1:1). Serum medium (SFM), and add 20ng / mL epidermal growth factor (EGF, Invitrogen Company), 10ng / mL human basic fibroblast growth factor (hFGFb, Invitrogen Company) and 2% B-27 (Gibco), Lasts 14-21 days. After gentle centrifugation for spheroid formation, replace SFM every 3 days. Spheroids were collected and dissociated enzymatically (with 0.05% trypsin in 0.53 mM EDTA-4Na for 15 minutes at 37°C). Cells were then stained with Hoechst 33342 (Solarbio) and re-sorted by FAC...

Embodiment 2

[0057] Example 2 Cell Viability Detection and Drug Half Inhibition Rate Calculation

[0058] The half inhibitory rate (IC) of the drug on the cells 50 ) was calculated from the results of cell viability assays. Collect various cell lines in the logarithmic growth phase according to 2×10 5 Cells / mL concentration was inoculated in a 96-well plate, each well was inoculated with 100 μL, and 6 replicate wells were set up in each group. After overnight culture (24 h) according to the culture conditions of various types of cells, different concentrations of artemisinin and other drugs were added to treat for 24 h. Cell viability was detected by conventional MTT (Sigma company) method.

[0059] The detection results of artemisinin and conventional chemotherapy drugs on tumors and stem cells are shown in Table 1. Conventional chemotherapy drugs such as sorafenib, doxorubicin, cisplatin, paclitaxel, fluorouracil, and gemcitabine have much lower killing effects on tumor stem cells than...

Embodiment 3

[0064] Example 3 Artemisinin on MDA-MB-231 and its stem cell morphology

[0065] The MDA-MB-231 cells and their stem cells in the logarithmic growth phase were inoculated in a six-well plate, added with 300 μg / mL artemisinin, and cultured for 24 hours. After taking it out, they were washed three times with pH 7.4 PBS buffer, and examined under an optical microscope (Primovert , Carl Zeiss Company) to observe and take pictures. The results are attached image 3 As shown, artemisinin has no obvious effect on the morphology of MDA-MB-231 cells, but has a more obvious effect on the morphology of MDA-MB-231 stem cells. The morphological changes indicate that MDA-MB-231 stem cells are killed by artemisinin.

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Abstract

The invention discloses application of artemisinin in the preparation of drugs to inhibit or kill breast carcinoma stem cells. Artemisinin can kill breast carcinoma stem cells effectively, can betterkill tumor stem cells than carcinoma cells experiencing no stem evolution, and has selective efficient killing effect against tumor stem cells. Artemisinin can induce 'ferroptosis' of breast carcinomastem cells. By the use of artemisinin with Fe3O4 nano particles, and alternatively further coupling the magnetic nanoparticles with targets, such as tyrosine kinase-like orphan receptor 1 antibody, the effect of killing breast carcinoma stem cells is improved significantly. The invention also discloses an antitumor drug composition to inhibit or kill breast carcinoma stem cells. A new strategy isprovided for tumor therapy to specifically kill tumor stem cells; the application herein is important to the improvement of tumor treatment effect, the reduction of tumor recurrence, the improvementof survival quality of tumor patients and the extending of survival time.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to the application of artemisinin in cancer treatment drugs for killing breast cancer stem cells. Background technique [0002] Cancer stem cells, also known as tumor-initiating cells, are a type of cell population in tumors that have the ability to self-renew and generate heterogeneous tumor cells. At present, the clinical methods for treating tumors can kill most of the tumor cells in a short period of time and make the tumor shrink rapidly, but they cannot fundamentally cure the tumor. Because these therapies are mainly aimed at most of the differentiated cells in tumor tissue, rather than tumor stem cells. Even if the vast majority of tumor cells are killed, as long as there are surviving tumor stem cells, tumor recurrence and metastasis will still be caused. At present, most of the clinical anti-tumor treatments can not produce a good killing effect on tumor stem cells, and ...

Claims

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Application Information

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IPC IPC(8): A61K31/366A61K33/26A61P35/00
Inventor 张薇吴旸徐迪梁明星丁莉唐金海
Owner JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV
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