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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  • 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-t

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
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Example Embodiment

[0053] Example 1 Tumor stem cell induction and spheroidization experiment

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

[0055] The HepG2, MNNG / HOS, SKOV-3, BT474, A549, MCF-7, BGC-823, MDA-MB-231, T47D cells are divided into 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 DMEM / Ham nutrient mixture F-12 (1:1). Serum medium (SFM), and add 20ng / mL epidermal growth factor (EGF, Invitrogen), 10ng / mL human basic fibroblast growth factor (hFGFb, Invitrogen) and 2% B-27 (Gibco), Lasts 14-21 days. After the gentle centrifugal sphere is formed, the SFM is replaced every 3 days. Spherical cells were collected and dissociated enzymatically (using 0.05% trypsin, containing 0.53mM EDTA-4Na, 15 minutes, 37°C). The cells were then stained with Hoechst 33342 (Solarbio) and re-sorted by FACS to d...

Example Embodiment

[0057] Example 2 Detection of cell viability and calculation of drug half inhibition rate

[0058] The half inhibition rate of the drug on the cell (IC 50 ) Is calculated from the cell viability test results. Collect all kinds of cell lines in the logarithmic growth phase according to 2×10 5 Cells / mL were inoculated in 96-well plates, 100μL per well, 6 multiple wells were set up in each group, after overnight culture (24h) according to the culture conditions of various types of cells, after adding different concentrations of artemisinin and other drugs for 24h, Use conventional MTT (Sigma) method to detect cell activity.

[0059] The detection results of artemisinin and conventional chemotherapy drugs on tumors and their stem cells are shown in Table 1. The killing effects of conventional chemotherapy drugs such as sorafenib, adriamycin, cisplatin, paclitaxel, fluorouracil, gemcitabine, etc. on tumor stem cells are much lower than Normal cancer cells, while artemisinin has a selec...

Example Embodiment

[0064] Example 3 The effect of artemisinin on the morphology of MDA-MB-231 and its stem cells

[0065] The MDA-MB-231 cells and their stem cells in the logarithmic growth phase were seeded in a six-well plate, 300μg / mL artemisinin was added and cultured for 24 hours. After removal, the cells were washed with pH 7.4 PBS buffer for 3 times, and then examined in a light microscope (Primovert , Carl Zeiss) under observation and photographs. 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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