CN107744518A - Application of the Etomoxir in terms of colorectal cancer is treated - Google Patents
Application of the Etomoxir in terms of colorectal cancer is treated Download PDFInfo
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- CN107744518A CN107744518A CN201711250041.6A CN201711250041A CN107744518A CN 107744518 A CN107744518 A CN 107744518A CN 201711250041 A CN201711250041 A CN 201711250041A CN 107744518 A CN107744518 A CN 107744518A
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- colorectal cancer
- etomoxir
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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
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Abstract
The invention discloses application of the Etomoxir in terms of colorectal cancer is treated.Specifically Etomoxir is preparing intestinal cancer protective agents, especially suppresses the application in terms of the medicine of intestinal cancer transfer.Present invention research display, Etomoxir can significantly inhibit the Clone formation under colorectal cancer cell mistake nest, promote colorectal cancer cell anoikis, suppress the transfer ability of colorectal cancer cell in vivo, there is significant therapeutic effect to colorectal cancer, especially suppress the significant effect of colorectal cancer transfer, therefore available for the treatment of colorectal cancer transfer.The present invention provide not only a kind of new opplication of Etomoxir, expand the clinical practice field of Etomoxir, and the treatment for colorectal cancer transfer provides a kind of new therapy approach, has good popularizing application prospect.
Description
Technical field
The invention belongs to pharmaceutical technology field.More particularly, to application of the Etomoxir in terms of colorectal cancer is treated.
Background technology
Colorectal cancer is gastroenteric tumor common in world wide, is ranked first in the various malignant tumours in China, is complete
One of Etiological of causing death in the range of ball, and very big difficulty be present in clinical treatment.
The incidence and the death rate of colon cancer are higher, and the doctor in the field is similarly tired by tumor drug resistance problem in chemotherapy
Disturb.Estimate according to American Cancer Society, the tumor patient for dying from different degrees of resistance accounts for more than 90%, and the resistance problems of tumour are
Through the key factor as chemotherapy of tumors success or not.The front-line chemotherapeutic agents oxaliplatin that guide is recommended, is the most frequently used change
Treat one of medicine.But its chemical therapeutic effect still has much room for improvement, significant portion reason will also be attributed to cause because of resistance
Recurrence and transfer.
Etomoxir is a kind of carnitine palmityl transferase 1A（CPT1A）Inhibitor, have suppress aliphatic acid oxygen
The effect of change, Etomoxir is initially studied as Remedies for diabetes, while also has clinical test to prove that Etomoxir can
To improve the Left Ventricular Ejection Fraction of the patient of heart failure, cardiac output and clinical symptoms.
The content of the invention
The technical problem to be solved in the present invention be the defects of overcoming existing treatment of colorectal cancer medicine and deficiency and second not
The application limitation of gram house, there is provided a kind of medicine of new treatment colorectal cancer, i.e., Etomoxir is in terms for the treatment of of colorectal cancer
New opplication.
It is an object of the invention to provide application of the Etomoxir in terms for the treatment of of colorectal cancer medicine is prepared.
Above-mentioned purpose of the present invention is achieved through the following technical solutions：
Studies have shown that Etomoxir of the present invention can significantly inhibit the Clone formation under colorectal cancer cell mistake nest, promote knot straight
Colon-cancer cell anoikis, suppress the transfer ability of colorectal cancer cell in vivo, there is significant treatment to imitate to colorectal cancer
Fruit, especially suppress the significant effect of colorectal cancer transfer, therefore available for the treatment of colorectal cancer transfer.
Therefore, application of the Etomoxir in terms of intestinal cancer protective agents are prepared, and in the medicine for preparing suppression intestinal cancer transfer
The application in object space face, all should be within protection scope of the present invention.
Particularly preferably, the intestinal cancer is colorectal cancer.
It is highly preferred that the colorectal cancer is Ι II to IV phase colorectal cancers.
It is highly preferred that the colorectal cancer refers to human colon cancer cell HCT 15 or human colon adenocarcinoma cell HCT116.
In addition, said medicine is the medicine for referring to suppress colorectal cancer cell survival and/or growth.Specifically suppress knot
Rectum cancer cell loses the Clone formation under nest.
Said medicine may also mean that the medicine that can promote colorectal cancer cell apoptosis.Specifically promote colorectal cancer cell
Anoikis.
Said medicine may also mean that the medicine that can suppress colorectal cancer cell transfer.Suppress colorectal cancer cell in body
The medicine of interior transfer ability.
In addition, include the medicine of the treatment colorectal cancer of Etomoxir and pharmaceutically acceptable carrier or suppress knot directly
The medicine of intestinal cancer transfer, also should be within protection scope of the present invention.
Further, the medicine can also include its pharmaceutically acceptable carrier etc..
The invention has the advantages that：
The invention provides a kind of new opplication of Etomoxir, that is, is applied to treatment colorectal cancer, especially suppresses colorectal cancer
Transfer, Etomoxir can significantly inhibit the Clone formation under colorectal cancer cell mistake nest, promote colorectal cancer cell to lose nest and wither
Die, suppress the transfer ability of colorectal cancer cell in vivo, there is the effect of notable to colorectal cancer transfer, it is straight to can be applied to knot
In terms of the treatment of intestinal cancer transfer.
The present invention is not only that the treatment of colorectal cancer transfer provides a kind of new medicine and therapy approach, is also second
The application of Mack house provides new field.
Brief description of the drawings
Fig. 1 is the influence that Etomoxir is formed to colorectal cancer cell soft-agar cloning.
Fig. 2 is influence of the Etomoxir to colorectal cancer cell anoikis.
Fig. 3 is influence of the Etomoxir to Lung metastases in colorectal cancer cell nude mouse.
Fig. 4 is influence of the Etomoxir to nude mice body weight.
Embodiment
The present invention is further illustrated below in conjunction with Figure of description and specific embodiment, but embodiment is not to the present invention
Limit in any form.Unless stated otherwise, the reagent of the invention used, method and apparatus routinely try for the art
Agent, method and apparatus.
Unless stated otherwise, following examples agents useful for same and material are purchased in market.
The influence that the Etomoxir of embodiment 1 is formed to colorectal cancer cell soft-agar cloning
1st, experiment material
（1）Medicine：Etomoxir.
（2）Colorectal cancer cell：Human colon cancer cell HCT 15 and human colon adenocarcinoma cell HCT116.
（3）Soft agar purchased in market.
2nd, experiment packet
（1）Control group：Blank control, i.e. cancer cell are without any drug-treated.
（2）Experimental group：Cancer cell is handled using Etomoxir.
3rd, soft-agar cloning forms influence of the experiment detection Etomoxir to colorectal cancer cell Clone formation
（1）Soft agar is completed in six orifice plates, adds colorectal cancer cell, after its solidification, adds DMSO（Compare）And
50 μM, 100 μM of Etomoxir processing cell 3 weeks, then pass through micro- sem observation cell clonal formation situation.
Specific method is as follows：
1）After 1.4% agarose autoclave sterilization, mix, added in 6 orifice plates with 2 × 1640 culture mediums, per hole 2mL.
2）After 0.7% agarose autoclave sterilization, mixed with 2 × 1640 culture mediums, by the HCT of exponential phase
After 15 and HCT116 cells are digested with pancreatin, 4 × 10 are taken4Cell is resuspended with mixed culture medium, is uniformly spread after solidification
On agarose media.
3）1mL1640 culture mediums are added in the top, DMSO is separately added into culture medium（Compare）And 50 μM, 100 μM
Etomoxir, liquid was changed every 3 days 1 time.
4）After 3 weeks, micro- Microscopic observation Clone formation situation, and statistics clone's number of taking pictures.
（2）Experimental result
As a result as shown in figure 1, after being handled using Etomoxir, the clone that colorectal cancer cell is formed in soft agar substantially subtracts
It is few, show that Etomoxir can suppress the survival and growth under colorectal cancer cell mistake nest.
Influence of the Etomoxir of embodiment 2 to colorectal cancer cell anoikis
1st, experiment material
（1）Medicine：With embodiment 1.
（2）Cancer cell：With embodiment 1.
（3）Apoptosis kit purchased in market.
2nd, the anoikis situation of HCT15 and HCT116 cells after being handled by Flow cytometry Etomoxir
（1）It is low stick colorectal cancer cell is completed in 6 orifice plates, addition contains DMSO（Compare）And 50 μM, 100 μM of second not
Gram house medium treatment cell, then after 72h pass through apoptosis kit detect anoikis situation.
Specific method is as follows：
1）After HCT15 the and HCT116 cells of exponential phase are digested with pancreatin, 1 × 10 is taken6Cell, which is taped against, low sticks 6 orifice plates
In.
2）Addition contains DMSO（Compare）And 50 μM, the medium treatment cell of 100 μM of Etomoxir.
3）Cell is collected after 72h, cell, Annexin V are handled according to the method for apoptosis detection kit after pancreatin digestion
Pass through flow cytomery Apoptosis situation after being completed with PI dyeing.
（2）Experimental result
As a result as shown in Fig. 2 the percentage shown in Fig. 2 is Annexin V positive（The cell of apoptosis occurs）Ratio.Knot is straight
After Etomoxir is handled, anoikis substantially increases colon-cancer cell, shows that Etomoxir can remarkably promote colorectal cancer
Cell anoikis.
Colorectal cancer cell is shifted the Etomoxir of embodiment 3 and the influence of nude mice body weight
1st, experiment material
（1）Medicine：With embodiment 1.
（2）Colon and rectum cell：With embodiment 1.
（3）Nude mice purchased in market.
2nd, after detecting Etomoxir processing by the transfer nude mice model of tail vein injection, to HCT15 and HCT116 cells
The influence shifted in vivo
（1）The Metastatic nude model of tail vein injection HCT15 and HCT116 cell construction colorectal cancer, with 40mg/kg second not
Gram house processing cell, influence of the detection Etomoxir to being shifted in colorectal cancer cell body.
Specific method is as follows：
1）After the HCT15 of exponential phase and the cells of HCT 116 are digested with pancreatin, 2 × 10 are taken6100 microlitres of PBS weights of cell
It is outstanding.
2）By 2 × 106HCT15 and HCT116 cell infusions to nude mice tail vein.
3）Start within 2nd day, 40mg/kg Etomoxir is injected to nude mice abdominal cavity, injected every other day once.
4）Nude mice is weighed week about.
5）After 8 weeks, nude mice to be implemented to be euthanized, takes out nude mice lungs, paraformaldehyde solution is fixed, and HE is dyed after section,
Taken pictures under microscope and count Lung metastases tubercle number.
（2）Experimental result
As a result as shown in Figure 3 and Figure 4, in colorectal cancer cell Metastatic nude model, after Etomoxir is handled, Lung metastases knot
Section number is decreased obviously, and nude mice body weight shows that Etomoxir can significantly suppress colorectal cancer cell and exist without significant change
Internal transfer ability simultaneously has no significant effect to nude mice body weight.
Above-described embodiment is the preferable embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any Spirit Essences without departing from the present invention with made under principle change, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (10)
1. application of the Etomoxir in terms of intestinal cancer protective agents are prepared.
2. application of the Etomoxir in terms of the medicine for suppressing intestinal cancer transfer is prepared.
3. application according to claim 1 or 2, it is characterised in that the intestinal cancer is colorectal cancer.
4. application according to claim 3, it is characterised in that the colorectal cancer is Ι II to IV phase colorectal cancers.
5. application according to claim 3, it is characterised in that the colorectal cancer refers to human colon cancer cell HCT 15
Or human colon adenocarcinoma cell HCT116.
6. application according to claim 1 or 2, it is characterised in that the medicine is to refer to suppress colorectal cancer cell
Survival and/or the medicine of growth.
7. application according to claim 1 or 2, it is characterised in that the medicine is to refer to promote colorectal cancer cell
The medicine of apoptosis.
8. application according to claim 1 or 2, it is characterised in that the medicine is to refer to suppress colorectal cancer cell
The medicine of transfer.
9. a kind of medicine for treating colorectal cancer, it is characterised in that include Etomoxir and pharmaceutically acceptable carrier.
10. a kind of medicine for suppressing colorectal cancer transfer, it is characterised in that include Etomoxir and pharmaceutically acceptable load
Body.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711250041.6A CN107744518B (en) | 2017-12-01 | 2017-12-01 | Application of pemetrexed in treating colorectal cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711250041.6A CN107744518B (en) | 2017-12-01 | 2017-12-01 | Application of pemetrexed in treating colorectal cancer |
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| Publication Number | Publication Date |
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| CN107744518A true CN107744518A (en) | 2018-03-02 |
| CN107744518B CN107744518B (en) | 2020-05-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201711250041.6A Active CN107744518B (en) | 2017-12-01 | 2017-12-01 | Application of pemetrexed in treating colorectal cancer |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110227159A (en) * | 2018-03-05 | 2019-09-13 | 义慧科技(深圳)有限公司 | The drug and CPT1a inhibitor for improving entity tumor confrontation blood vessel drug eluting drug resistance are in application wherein |
| 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 |
| WO2021108923A1 (en) * | 2019-12-05 | 2021-06-10 | Bold Therapeutics Inc. | Combined use of sodium trans-[tetrachloridobis(1h-indazole)ruthenate(iii)] and etomoxir for treating cancers |
| CN113143932A (en) * | 2021-04-15 | 2021-07-23 | 东莞市人民医院 | Application of Esarapip as anti-colorectal cancer drug |
-
2017
- 2017-12-01 CN CN201711250041.6A patent/CN107744518B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| EMMA HERNLUND等: "Potentiation of chemotherapeutic drugs by energy metabolism inhibitors 2-deoxyglucose and etomoxir", 《INTERNATIONAL JOURNAL OF CANCER》 * |
| ZAYTSEVA, YEKATERINA等: "Inhibition of fatty acid synthase reduces mitochondrial respiration and addiction of colorectal cancer cells to glycolysis", 《CANCER RESEARCH》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110227159A (en) * | 2018-03-05 | 2019-09-13 | 义慧科技(深圳)有限公司 | The drug and CPT1a inhibitor for improving entity tumor confrontation blood vessel drug eluting drug resistance are in application wherein |
| 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 |
| WO2021108923A1 (en) * | 2019-12-05 | 2021-06-10 | 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 |
| CN113143932A (en) * | 2021-04-15 | 2021-07-23 | 东莞市人民医院 | Application of Esarapip as anti-colorectal cancer drug |
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| Publication number | Publication date |
|---|---|
| CN107744518B (en) | 2020-05-26 |
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