CN105982883A - Application of palmitic acid to preparation of drug for treating colon cancer - Google Patents

Application of palmitic acid to preparation of drug for treating colon cancer Download PDF

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Publication number
CN105982883A
CN105982883A CN201510087609.1A CN201510087609A CN105982883A CN 105982883 A CN105982883 A CN 105982883A CN 201510087609 A CN201510087609 A CN 201510087609A CN 105982883 A CN105982883 A CN 105982883A
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China
Prior art keywords
palmitic acid
colon cancer
acid
application
cancer
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Pending
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CN201510087609.1A
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Chinese (zh)
Inventor
申华莉
王真昕
林灵
杨芃原
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Fudan University
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Fudan University
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Priority to CN201510087609.1A priority Critical patent/CN105982883A/en
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Abstract

The invention belongs to the technical field of new application of compounds and relates to new pharmaceutical application of palmitic acid, in particular to application of the palmitic acid to preparation of a drug for treating colon cancer and resisting colon cancer metastasis. Through an in-vitro CCK-8 antitumor activity evaluation test, the result shows that the palmitic acid has a remarkable inhibiting effect on growth of human colon cancer cell strains SW-480 and SW-620 with different metastasis potentials and particularly has a remarkable inhibiting effect on the movement and migration capability of SW-620 with a high metastasis potential. Furthermore, the palmitic acid can be used for preparing the drug for resisting colon cancer and colon cancer metastasis and has good development and application prospects.

Description

Palmic acid application in preparation treatment colon cancer drug
Technical field
The invention belongs to compound new application technical field.The medicine relating to Palmic acid (Palmitic Acid) is new Purposes, is specifically related to Palmic acid (Palmitic Acid) at preparation treatment colon cancer and inhibitor against colon carcinoma cells diversion medicaments In application.
Background technology
Report discloses colon, and a cancer is a malignant tumor, shows according to 2012 annual datas: the U.S. estimated 143460 Example newly sends out colon cancer cases, and has 51690 example deaths.America and Europe, colon cancer have become as occupy pulmonary carcinoma and 3rd the cancer-related disease causing death after breast carcinoma.And Chinese Anti-Cancer Association colon cancer professional committee member Meeting (CACA) data show: the sickness rate of colorectal cancer is risen to 2009 by 20.4 examples/100,000 people of 1999 36.2 examples/100,000 people in year, increase by 6.2% every year on average.The sickness rate of China in 2007 is 29.62 examples / 10 ten thousand, mortality rate is 14.15 examples/100,000.Even more noteworthy, its sickness rate and death up to now Rate is the most in rising trend.Know together in the industry and capture cancer at present and have two big targets: one is " not giving birth to cancer ", i.e. studies Normal cell becomes reason and the mechanism of cancerous cell, and is prevented;Two is " allowing cancer not shift ", and transfer is shadow Ring the primary factor of patient life cycle, shifted during the malignant tumor patient ID of about more than 60%. If solving this problem, cancer, i.e. as benign tumor, can be cured.There is researcher by " cancerometastasis " It is classified as one of urgent significant problem highly necessary solved of life sciences in this century;Transfer is that colon cancer is low equally cures height extremely The main cause died, however existing to change and the Effect study of phospholipid metabolism in colon cancer transfer process about field The most blank.
Known fatty acid has metabolic function widely, is possible not only to, presented in free fatty acid, also may be used To constitute the lipoid substance of Various Complex.In human body, fatty acid may be constructed triacylglycerol and stores energy, May be constructed phospholipid and become the phospholipid bilayer of cell membrane, can as second message,second messenger (DAG, PIP2, LPA etc.) participate in signal conduction, it is also possible to the expression of gene is affected as the part of nuclear receptor.It is reported, very Many diseases are all relevant with disorders of lipid metabolism, such as: diabetes, obesity, senile dementia, cancer etc., therefore, The change of content of fatty acid has important impact, lipid material and metabolic process thereof in life entity to health Research become disease pathogenesis and diagnoses and treatment and one of the emphasis problem of medicine R&D process.
Research display, the lipid composition of cell membrane and mobility are to maintaining cell topology, motor capacity, film Connection protein active and the holding normal physiological function of cell have important impact,
The present invention, based on the fat group examination research carrying out colon cancer transfer cell line, intends providing Palmic acid The new medicine use of (Palmitic Acid), is specifically related to Palmic acid (Palmitic Acid) at preparation treatment knot Application in intestinal cancer and inhibitor against colon carcinoma cells diversion medicaments.
The prior art relevant with the application has:
[1] Siegel R, Naishadham D, Jemal A.Cancer statistics, 2013.CA Cancer J Clin 2013; 63:11-30.
[2] Jemal A, Bray F, Center MM, et a1.Global cancer statistics.CA:a cancer journal for clinicians 2011;61 (2): 69-90.
[3] Desantis C, naishadham D, Jemal A.Cancer Statistics for African American, 2013. CA Cancer J Clin 201363:151-166.
[4] Corley, Douglas A., Christopher D.Adenoma Detection Rate and Risk of Colorectal Cancer and Death.New England Journal of Medicine 2014 (14): 1298-1306.
[5] Hirsch HA, Iliopoulos D, Joshi A, et a1.A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases.Cancer cell 2010;17 (4): 348-361.
[6] Nguyen HP, Schug KA.The advantages of ESI-MS detection in conjunction with HILIC mode separations:Fundamentals and applications.Journal of separation science 2008;31 (9): 1465-1480.
[7] Falconer J, Ross J, Fearon K, et a1.Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines.British journal of cancer 1994;69 (5): 826-832.
[8] Anneken DJ, Both S, Christoph R, et a1.Fatty Acids.Ullmann ' s Encyclopedia of Industrial Chemistry 2006;Published Online, DOI:10.1002/14356007.al0_245.pub2.
Summary of the invention
It is an object of the invention to the important shadow to life entity disease incidence based on current lipid material and metabolism thereof Ring, cure high dead present situation especially for colon cancer is low, it is provided that the medicine of Palmic acid (Palmitic Acid) New application, is specifically related to Palmic acid (Palmitic Acid) at preparation treatment colon cancer and inhibitor against colon carcinoma cells transfer medicine Application in thing.
The present invention is based on high flux, high-resolution, high-precision lipid isolation identification technology and bioinformatics work Sign an undertaking conjunction, represent lipid express spectra difference in the case of colon cancer metastatic potential is incremented by panoramically;Based on this, Colon cancer transfer cell line carries out fat group examination further, and result shows, containing Palmic acid (Palmitic Acid) Phospholipid expression in colon cancer cell and transitivity colon cancer cell present reduction trend, it was demonstrated that, Ke Yitong Cross additional Palmic acid (Palmitic Acid) and kill tumor cell, the Invasion and Metastasis of suppression tumor.
Concrete, the present invention is tested by vitro CCK-8 antitumor activity evaluation, and result shows, Palmic acid The growth of the human colon cancer cell strain SW-480, SW-620 of Metastatic potential is had by (Palmitic Acid) There is significant inhibitory action;Palmic acid (Palmitic Acid) is especially to the SW-620 with high metastatic potential Motion and transfer ability there is significant inhibitory action, therefore, Palmic acid (Palmitic Acid) can be used for Prepare inhibitor against colon carcinoma cells and inhibitor against colon carcinoma cells diversion medicaments.
More specifically, the invention provides the new application of compound Palmic acid (Palmitic Acid), especially The Palmic acid (Palmitic Acid) purposes in preparation treatment colon cancer and inhibitor against colon carcinoma cells diversion medicaments.
Compound Palmic acid of the present invention (Palmitic Acid) No. cas: 57-10-3, molecular formula: C16H32O2, shown in structure such as formula (I):
In the present invention, use shotgun technology CCL188 SW-480 to two kinds of Metastatic potentials (low metastatic potential), SW-620 (high metastatic potential) carry out lipid composition analysis, and result shows, containing Petiolus Trachycarpi The phospholipid of acid (Palmitic Acid) compares low metastatic potential cell line in high metastatic potential cell line SW0620 In SW-480, content has reduction;
In the present invention, being tested by vitro CCK-8 antitumor activity evaluation, result shows, Palmic acid (Palmitic Acid) to human colon cancer cell strain SW-480, the growth of SW-620 has a significant inhibitory action, further, Described Palmic acid (Palmitic Acid) can be used for preparing inhibitor against colon carcinoma cells and inhibitor against colon carcinoma cells diversion medicaments, and tool There is good development prospect.
It is an advantage of the current invention that:
1, present invention firstly discloses Palmic acid (Palmitic Acid) at preparation treatment colon cancer and inhibitor against colon carcinoma cells New application in diversion medicaments;Up to now, there is not yet Palmic acid (Palmitic Acid) and there is resistive connection intestinal The research report of the activity of cancer and inhibitor against colon carcinoma cells transfer;
2, the present invention comes from the lipidomics screening carrying out colon carcinoma cell line, does not exist and is changed by other Compound provides the possibility of any prompting, simultaneously described in Palmic acid for the treatment of colon cancer, there is significantly effect Really.
By concrete drawings and Examples, the present invention will be described in detail in order to make it easy to understand, following. It is important to note that instantiation and accompanying drawing are merely to explanation, it is clear that those of ordinary skill in the art According to illustrating herein, within the scope of the invention the present invention can be made various correction and change, this A little corrections and change are also included in the scope of the present invention.It addition, the present invention refer to open source literature, these documents Being to more clearly describe the present invention, their entire contents is all included in and is carried out reference herein, just looks like them Full text repeated description the most in this article excessively as.
Accompanying drawing explanation
SW-480 and the SW-620 cell of Fig. 1: the present invention is containing variable concentrations Palmic acid (Palmitic Acid) Culture medium culturing under growth curve.
Detailed description of the invention
The preparation method of compound Palmic acid (Palmitic Acid) involved in the present invention sees prior art literary composition Offer8
Embodiment 1: prepare compound Palmic acid (Palmitic Acid) tablet or capsule
Taking 20 g of compound Palmic acids (Palmitic Acid), the customary adjuvant 180 grams of tablet is prepared in addition, Mixing, conventional tablet presses makes 1000;Or,
Taking 20 g of compound Palmic acids (Palmitic Acid), the customary adjuvant such as starch of capsule is prepared in addition 180 grams, mixing, encapsulated make 1000;
Use CCK-8 method to evaluate Palmic acid (Palmitic Acid) growth inhibited of human colon cancer cell strain is made With and pharmaceutically active:
Taking the logarithm, (cell derived is in the attached tumor of Fudan University for cell SW-480 and SW620 to be measured of trophophase Hospital), it is inoculated in 96 orifice plates, inoculating cell concentration is 2000 cells/well, and process group adds not consubstantiality Long-pending Palmic acid (Palmkic Acid) diluent, makes final concentration be respectively 0 μM, 50 μMs, 100 μMs, and 200 μM and 300 μMs;CCK-8 method analyzes the cell viability of different time points (1d, 3d, 5d, 7d), often Individual time point detects 6 multiple holes respectively, adds 10 μ L CCK-8 cell proliferation and activity in the testing sample of every hole Detectable (colleague chemical company of Japan product), CCK-8 reagent is hatched in incubator altogether with cell to be measured 2h, then detects by microplate reader (Thermo Products), a length of 450nm of excitation light wave, launches The a length of 630nm of light wave, 96 orifice plates are read plate, are recorded A450Light absorption value, A630For corrected value;Light absorption value measures Rear drafting cell proliferation curve, compares the change of different experiments group growth curve;
Result shows: along with the increase successively of Palmic acid (Palmitic Acid) concentration, SW-480 in culture medium Slowing down gradually with the speed of growth of SW-620, depression effect is the strongest in SW-620 cell line, supplements Palmic acid (PalmiticAcid) can suppress the multiplication capacity (as shown in Figure 1) of colon cancer cell;
Above-mentioned test result indicate that, Palmic acid (Palmitic Acid) to human colon cancer cell strain SW-480, The growth of SW-620 has significant inhibitory action;Motion especially for the SW-620 of high metastatic potential All there is significant inhibitory action with transfer ability;Therefore, described Palmic acid (Palmitic Acid) can be used In preparing inhibitor against colon carcinoma cells and the medicine of inhibitor against colon carcinoma cells transfer, it has good development prospect.

Claims (3)

1. the Palmic acid (Palmitic Acid) purposes in preparation treatment colon cancer drug;
Described compound Palmic acid No. cas: 57-10-3, molecular formula: C16H32O2, structure such as formula (I) Shown in:
2. the purposes as described in claim 1, it is characterised in that described Palmic acid (Palmitic Acid) For preparing the medicine of inhibitor against colon carcinoma cells transfer.
3. the purposes as described in claim 1, it is characterised in that described Palmic acid suppression human colon carcinoma is thin The growth of born of the same parents system SW-480 or SW-620, motion or transfer ability.
CN201510087609.1A 2015-02-17 2015-02-17 Application of palmitic acid to preparation of drug for treating colon cancer Pending CN105982883A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1251296A (en) * 1998-10-16 2000-04-26 杨振华 Use of anticancer material and production method of said anti-cancer material
CN1709284A (en) * 2005-06-23 2005-12-21 南京大学医学院附属鼓楼医院 Extraction of anti-tumour active ingredient fatty acid from ground beetle
CN104173325A (en) * 2013-12-04 2014-12-03 复旦大学 Application of palmitic acid in preparation of liver cancer treatment and liver cancer metastasis resistance medicines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1251296A (en) * 1998-10-16 2000-04-26 杨振华 Use of anticancer material and production method of said anti-cancer material
CN1709284A (en) * 2005-06-23 2005-12-21 南京大学医学院附属鼓楼医院 Extraction of anti-tumour active ingredient fatty acid from ground beetle
CN104173325A (en) * 2013-12-04 2014-12-03 复旦大学 Application of palmitic acid in preparation of liver cancer treatment and liver cancer metastasis resistance medicines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JOHN W. SALERNO等: "The use of sesame oil and other vegetable oils in the inhibition of human colon cancer growth in vitro.", 《ANTICANCER RES.》 *

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Application publication date: 20161005