CN107744518B - Application of pemetrexed in treating colorectal cancer - Google Patents
Application of pemetrexed in treating colorectal cancer Download PDFInfo
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- CN107744518B CN107744518B CN201711250041.6A CN201711250041A CN107744518B CN 107744518 B CN107744518 B CN 107744518B CN 201711250041 A CN201711250041 A CN 201711250041A CN 107744518 B CN107744518 B CN 107744518B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
Abstract
The invention discloses an application of an etomoxider in treating colorectal cancer. In particular to the application of the pemetrexed in preparing medicaments for preventing and treating intestinal cancer, in particular to medicaments for inhibiting intestinal cancer metastasis. The research of the invention shows that the nemock can obviously inhibit the clone formation of the colorectal cancer cells under the condition of losing nests, promote the anoikis of the colorectal cancer cells, inhibit the transfer capability of the colorectal cancer cells in vivo, and have obvious treatment effect on the colorectal cancer, especially obvious effect of inhibiting the colorectal cancer transfer, so the nemock can be used for treating the colorectal cancer transfer. The invention not only provides a new application of the Emock house, expands the clinical application field of the Emock house, but also provides a new treatment approach for treating colorectal cancer metastasis, and has good popularization and application prospects.
Description
Technical Field
The invention belongs to the technical field of medicines. More particularly, it relates to the use of etomox kennel for the treatment of colorectal cancer.
Background
Colorectal cancer is a common gastrointestinal tumor in the world, is the top of various malignant tumors in China, is one of the main causes of death of people in the world, and has great difficulty in clinical treatment.
The incidence and mortality of colon cancer are high, and doctors in the field also trouble the problem of tumor drug resistance in chemotherapy. According to the American cancer society, over 90% of patients who die from tumors with different degrees of drug resistance are treated, and the problem of drug resistance of tumors has become a key factor for the success of tumor chemotherapy. The first-line chemotherapeutic drug oxaliplatin, recommended by guidelines, is one of the most commonly used chemotherapeutic drugs. However, its chemotherapeutic effect remains to be improved, and is also due in large part to relapse and metastasis due to drug resistance.
The etomoxider is an inhibitor of carnitine palmitoyl transferase 1A (CPT 1A), has the effect of inhibiting fatty acid oxidation, is originally researched as a diabetes treatment medicament, and has clinical trials for proving that the etomoxider can improve the left ventricular ejection fraction, the cardiac output and the clinical symptoms of patients with heart failure.
Disclosure of Invention
The invention aims to solve the technical problems of overcoming the defects and shortcomings of the existing colorectal cancer treatment medicine and the application limitation of the Yimocksu, and provides a new medicine for treating colorectal cancer, namely the new application of the Yimocksu in the aspect of colorectal cancer treatment.
The invention aims to provide application of the pemetrexed in preparing medicaments for treating colorectal cancer.
The above purpose of the invention is realized by the following technical scheme:
the research of the invention shows that the nemock can obviously inhibit the clone formation of the colorectal cancer cells under the condition of losing nests, promote the anoikis of the colorectal cancer cells, inhibit the transfer capability of the colorectal cancer cells in vivo, and have obvious treatment effect on the colorectal cancer, especially obvious effect of inhibiting the colorectal cancer transfer, so the nemock can be used for treating the colorectal cancer transfer.
Therefore, the application of the pemetrexed in preparing the medicines for preventing and treating intestinal cancer and the medicines for inhibiting intestinal cancer metastasis are both within the protection scope of the invention.
Particularly preferably, the intestinal cancer is colorectal cancer.
More preferably, the colorectal cancer is stage i II to IV colorectal cancer.
More preferably, the colorectal cancer is human colon cancer cell HCT15 or human colon adenocarcinoma cell HCT 116.
In addition, the above-mentioned drug means a drug capable of inhibiting the survival and/or growth of colorectal cancer cells. In particular, the formation of clones under the condition of colorectal cancer cell anoikis is inhibited.
The above medicine can also be medicine for promoting colorectal cancer cell apoptosis. In particular to promoting the anoikis of colorectal cancer cells.
The above drug may also be a drug capable of inhibiting colorectal cancer cell metastasis. I.e. drugs that inhibit the metastatic ability of colorectal cancer cells in vivo.
In addition, drugs for treating colorectal cancer or drugs for inhibiting colorectal cancer metastasis, which comprise etomoxider and a pharmaceutically acceptable carrier, are also within the scope of the present invention.
Further, the medicament may further include a pharmaceutically acceptable carrier thereof and the like.
The invention has the following beneficial effects:
the invention provides a new application of the Etmock house, namely, the Etmock house is applied to treating colorectal cancer, in particular to inhibiting colorectal cancer metastasis, the Etmock house can obviously inhibit the clone formation of colorectal cancer cells under the condition of losing nests, promote the anoikis of the colorectal cancer cells, inhibit the metastatic capability of the colorectal cancer cells in vivo, has obvious curative effect on the colorectal cancer metastasis, and can be applied to the aspect of treating the colorectal cancer metastasis.
The invention not only provides a new treatment medicament and a new treatment way for the treatment of colorectal cancer metastasis, but also provides a new field for the application of the Etmockson.
Drawings
FIG. 1 is a graph of the effect of Emockson on the formation of soft agar clones of colorectal cancer cells.
FIG. 2 is a graph of the effect of Etomockel on anoikis in colorectal cancer cells.
FIG. 3 is a graph showing the effect of Emockson on lung metastasis in nude mice with colorectal cancer cells.
FIG. 4 is a graph showing the effect of Emox shepherd on body weight in nude mice.
Detailed Description
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
Example 1 Effect of Emox on the formation of Soft agar clones of colorectal cancer cells
1. Experimental Material
(1) Medicine preparation: the Emoxk house.
(2) Colorectal cancer cell: human colon cancer cell HCT15 and human colon adenocarcinoma cell HCT 116.
(3) Commercially available soft agar.
2. Experiment grouping
(1) Control group: blank control, i.e. cancer cells were not treated with any drug.
(2) Experimental groups: cancer cells were treated with etomox.
3. Soft agar clonogenic assay to examine the effect of Emockson on the clonogenic formation of colorectal cancer cells
(1) After the cells were coagulated, cells were treated with DMSO (i.e., control) and 50. mu.M and 100. mu.M Etomockel house for 3 weeks, and then observed for cell colony formation by microscope.
The specific method comprises the following steps:
1) 1.4% agarose was autoclaved, mixed with 2X 1640 medium, and added to 6-well plates at 2mL per well.
2) Sterilizing 0.7% agarose at high temperature under high pressure, mixing with 2 × 1640 culture medium, trypsinizing logarithmic growth phase HCT15 and HCT116 cells, and collecting 4 × 104The cells were resuspended in the mixed medium and spread evenly on the solidified agarose medium.
3) 1mL of 1640 medium was added to the top, and DMSO (i.e., control) and 50. mu.M and 100. mu.M etomox cells were added to the medium, and the medium was changed 1 time every 3 days.
4) After 3 weeks, the colony formation was observed under a microscope, and the number of colonies was counted by photographing.
(2) Results of the experiment
The results are shown in fig. 1, and the colonies formed by colorectal cancer cells in soft agar were significantly reduced after treatment with etomox, indicating that etomox can inhibit the survival and growth of colorectal cancer cells under anoikis.
Example 2 Effect of Etmockson on anoikis in colorectal cancer cells
1. Experimental Material
(1) Medicine preparation: the same as in example 1.
(2) Cancer cell: the same as in example 1.
(3) Commercially available apoptosis kits.
2. Detection of anoikis in HCT15 and HCT116 cells after Emockson treatment by flow cytometry
(1) Colorectal cancer cells were plated in low-adhesion 6-well plates, treated with media containing DMSO (i.e., control) and 50 μ M, 100 μ M etomox, and then assayed for anoikis by apoptosis kit after 72 h.
The specific method comprises the following steps:
1) subjecting HCT15 and HCT116 cells in logarithmic growth phase to trypsinization, and collecting 1 × 10 cells6Cells were plated in low-adhesion 6-well plates.
2) Cells were treated with medium containing DMSO (i.e., control) and 50. mu.M, 100. mu.M Etomogen.
3) And collecting cells after 72h, treating the cells according to the method of an apoptosis detection kit after pancreatin digestion, and detecting the apoptosis condition of the cells by a flow cytometer after Annexin V and PI staining is finished.
(2) Results of the experiment
The results are shown in FIG. 2, where the percentages shown in FIG. 2 are the proportion of Annexin V positive (i.e., cells undergoing apoptosis). After the colorectal cancer cells are treated by the Etomoke shed, anoikis is obviously increased, which shows that the Etomoke shed can obviously promote the anoikis of the colorectal cancer cells.
Example 3 Effect of Emockson on colorectal cancer cell metastasis and nude mouse body weight
1. Experimental Material
(1) Medicine preparation: the same as in example 1.
(2) Colorectal cell: the same as in example 1.
(3) Commercially available nude mice.
2. Effect of Emoke's treatment on in vivo transfer of HCT15 and HCT116 cells in nude mice model for transfer by tail vein injection
(1) Nude mouse metastasis model of colorectal cancer was constructed by tail vein injection of HCT15 and HCT116 cells, and the effect of Emockson on the in vivo metastasis of colorectal cancer cells was examined by treating the cells with 40mg/kg of Emockson.
The specific method comprises the following steps:
1) subjecting the cells of HCT15 and HCT116 in logarithmic growth phase to trypsinization, and collecting 2 × 10 cells6Cells were resuspended in 100 μ l PBS.
2) 2 x 10 to6The HCT15 and HCT116 cells of (a) were injected into the tail vein of nude mice.
3) Starting on day 2, 40mg/kg of etomox was injected into the abdominal cavity of nude mice every other day.
4) Nude mice were weighed every other week.
5) After 8 weeks, the nude mice were euthanized, the lungs of the nude mice were taken out, fixed with paraformaldehyde solution, sectioned and HE-stained, photographed under a microscope and counted for the number of lung metastasis nodules.
(2) Results of the experiment
The results are shown in fig. 3 and fig. 4, in the colorectal cancer cell nude mouse metastasis model, the number of lung metastasis nodules is obviously reduced after the treatment of the nemocs, and the body weight of the nude mouse has no obvious change, which indicates that the nemocs can obviously inhibit the metastatic capacity of the colorectal cancer cells in vivo and has no obvious influence on the body weight of the nude mouse.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (4)
1. The application of the pemukast in preparing the medicine for inhibiting colorectal cancer metastasis is characterized in that the colorectal cancer is colorectal cancer from stage I II to stage IV.
2. The use according to claim 1, wherein said colorectal cancer is human colon cancer cell HCT15 or human colon adenocarcinoma cell HCT 116.
3. The use of claim 1, wherein the medicament is a medicament capable of promoting apoptosis in colorectal cancer cells.
4. The use of claim 1, wherein the medicament is a medicament capable of inhibiting metastasis of colorectal cancer cells.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110227159B (en) * | 2018-03-05 | 2021-09-21 | 义慧科技(深圳)有限公司 | Medicine for improving drug resistance of solid tumor to anti-vascular drugs and application of CPT1a inhibitor in medicine |
| US20230024119A1 (en) * | 2019-12-05 | 2023-01-26 | Bold Therapeutics, Inc. | Combined use of sodium trans-[tetrachloridobis(1h-indazole)ruthenate(iii)] and etomoxir for treating cancers |
| CN111096962A (en) * | 2020-02-17 | 2020-05-05 | 中山大学附属第六医院 | Application of fatty acid oxidation inhibitor in preparation of medicine for treating colorectal cancer |
| CN113143932B (en) * | 2021-04-15 | 2022-10-04 | 东莞市人民医院 | Pharmaceutical application of Esarrapib serving as anti-colorectal cancer drug |
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Non-Patent Citations (2)
| Title |
|---|
| Inhibition of fatty acid synthase reduces mitochondrial respiration and addiction of colorectal cancer cells to glycolysis;Zaytseva, Yekaterina等;《CANCER RESEARCH》;20141031;第74卷(第19期);第43页全文 * |
| Potentiation of chemotherapeutic drugs by energy metabolism inhibitors 2-deoxyglucose and etomoxir;Emma Hernlund等;《INTERNATIONAL JOURNAL OF CANCER》;20081231;第123卷(第2期);第476-483页，特别是第476页左栏第1段，右栏第3-4段，第477页左栏第1段、右栏倒数第1段，第480页图4d、4e，第481页左栏第4段 * |
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