CN102824606B - Medicine for treating intestinal cancer and inhibiting formation of vascular mimicry of intestinal cancer and application of medicine - Google Patents
Medicine for treating intestinal cancer and inhibiting formation of vascular mimicry of intestinal cancer and application of medicine Download PDFInfo
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Abstract
The invention provides a medicine for treating intestinal cancer and inhibiting formation of vascular mimicry of the intestinal cancer. The medicine is prepared from the following crude drugs in parts by weight: 6-12 parts of curcuma zedoary, 10-20 parts of astragalus mongholicus, 15-21 parts of climbing fig fruit, 25-35 parts of Chinese actinidia root and 10-20 parts of waxgourd seed. The invention also provides application of the medicine in preparing medicines for treating the intestinal cancer and inhibiting the formation of the vascular mimicry of the intestinal cancer. The medicine provided by the invention has the advantages that the medicine can be used for inhibiting the growth of the intestinal cancer and inhibiting the formation of the vascular mimicry of the intestinal cancer; as the medicine is made of pure traditional Chinese medicines, the medicine has no toxic and side effects and is low in price, and can be easily accepted by patients; the number of the crude drugs is small; the raw materials are rich; the preparation process is simple; no harm is generated to the environment; and the medicine is good in application prospect in the aspect of intestinal cancer treatment.
Description
Technical field
The present invention relates to a kind ofly treat intestinal cancer and suppress medicine and the application thereof that the intestinal cancer vascular mimicry forms, specifically, is a kind of Chinese patent medicine prepared as raw material by Chinese herbal medicine of take.
Background technology
Colorectal cancer is one of common cancer, and its global sickness rate has ranked the 2-3 position of tumor.The diagnosis early stage due to intestinal cancer is lower, most of once discovery, just belongs to middle and advanced stage, causes its mortality rate high.According to NCHS(national sanitary statistics center) statistical report of 2010 years, the intestinal cancer mortality rate accounts for the 2nd of all tumors, and 5 years survival rates of patients with terminal are only 8.1%.Although traditional operation, chemicotherapy and newer biological targeting treatment have certain curative effect, still have at present most of intestinal cancer especially intestinal cancer shift and can not get effective control, therefore, improve curative effect and be still intestinal cancer treatment problem demanding prompt solution.
Tumor growth relies on the tumor microcirculation, thus suppress that the tumor microcirculation reduces or blocking-up tumor cell blood for being one of most important research direction of antitumor.For many years, people focus mostly on the tumor-blood-vessel growth of endotheliocyte dependence to the microcirculatory understanding of tumor, developed thus some and comprised the vascular targeting agents of colorectal cancer, but clinical efficacy is barely satisfactory.1999 vascular mimicry (Vascular Mimicry, VM) the research that is found to be new direction is provided.Fully different from classical tumor vessel structure, VM is that high aggressive tumor cell is in order to meet self blood confession, reinventing by self phenotype a kind of blood vessel sample pipeline formed with the reconstruct extracellular matrix, is to take a kind of brand-new microcirculation pattern that tumor cell is Constituent cell.Many studies confirm that, the growth of VM and tumor, differentiation, transfer and bad clinical prognosis have close relationship, the not good reason of vascular targeting agents clinical efficacy that had pragmatize of VM.Up to now, comprise the existence of all having found VM in most of tumors of colorectal cancer, therefore, the treatment of paying attention to VM in following intestinal cancer treatment will be expected to obtain good efficacy.At present, VM there is no effective Therapeutic Method and medicine, and research is still in foundation phase.
Chinese medicine is the important component part of intestinal cancer Comprehensive Treatment, and its curative effect is extensively approved, at tumor VM, there is no under the background of effective solution, and finding the method that solves intestinal cancer VM from Chinese medicine is to be worth a paths of exploring.The traditional Chinese medical science thinks, intestinal cancer belongs to gathers category, and pathogenesis is vital QI being weakened and pathogen being violent, simulataneous insufficiency and excessive.Weakened body resistancely take insufficiency of the spleenly as main, be essentially many doctors and generally acknowledge; And the domination of pathogen mostly is blood stasis, phlegm-damp, pyretic toxicity, wherein blood stasis more many doctors emphasize, as the Gao Bingjun of the Qing Dynasty points out in " Yangke Xinde Ji, Experience Gained in Treating External Diseases ": " carcinoma person, non-negative and positive lump that healthy energy is tied are the five internal organs blood stasis, and foul smell expectorant is stagnant to be formed ".Wang Qingren is thought: " tripe fu jie piece, blood clotting that must be tangible is poly-".Therefore, be summed up, the main pathomechanism of intestinal cancer is insufficiency of the spleen, and blood stasis has phlegm-damp or pyretic toxicity concurrently.But it is less to form relevant bibliographical information about the anti-intestinal cancer VM of Chinese medicine compound at present.
The 30th the 1st phase of volume of Chinese periodical " Anhui Chinese Medicine College journal ", in February, 2011, the paper of publishing " pressing down the impact of cancer side on mouse junction cancer transplanted tumor blood capillary and vascular mimicry formation ", disclose a kind of by Rhizoma Curcumae, Fructus Fici Pumilae, Radix Actinidiae Chinensis, Semen Benincasae, the Chinese medicine compound that Herba Portulacae forms has curative effect preferably to intestinal cancer, mice-transplanted tumor is had to certain inhibitory action, can suppress MV(Angiogenesis in colon cancer transplanted tumor, Microvascular) and the VM(vasculogenic mimicry, Vasculogenic Mimicry) formation, it may be one of mechanism of action pressed down the anti-intestinal cancer in cancer side.Chinese periodical " journal of shanghai Chinese medicine " the 45th the 1st phase of volume in 2011, the paper of publishing " pressing down the experimentation of cancer side to the effect of mice transplantability intestinal cancer ", confirmed to press down cancer side's (main component is Fructus Fici Pumilae, Radix Actinidiae Chinensis, Semen Benincasae, Rhizoma Curcumae, Herba Portulacae etc.) by zoopery the effect that suppresses mice intestinal cancer growth of xenografted and improve the mice with tumor life quality has been arranged, can promote apoptosis of tumor cells, this may be one of main mechanism pressed down the anti-intestinal cancer effect in cancer side.But the crude drug proportioning of above-mentioned paper unexposed this Chinese medicine compound.The present invention aims to provide a kind of mouse junction cancer transplanted tumor vascular mimicry that can suppress to a certain extent and forms, treats the significant medicine of intestinal cancer effect.
Summary of the invention
The objective of the invention is for deficiency of the prior art, provide a kind of and treat intestinal cancer and suppress the medicine that the intestinal cancer vascular mimicry forms.
One purpose more of the present invention is that a kind of purposes of said medicine is provided.
For achieving the above object, the technical scheme that the present invention takes is:
A kind of medicine for the treatment of intestinal cancer and suppressing the formation of intestinal cancer vascular mimicry, it is to be made by the crude drug of following weight portion: Rhizoma Curcumae 6-12 part, Radix Astragali 10-20 part, Receptaculum Fici Pumilae 15-21 part, Radix Actinidiae Chinensis 25-35 part, Semen Benincasae 10-20 part.
Described Rhizoma Curcumae is 8-10 part, and the described Radix Astragali is 13-17 part, and the described Receptaculum Fici Pumilae is 16-20 part, and described Radix Actinidiae Chinensis is 27-33 part, and described Semen Benincasae is 13-17 part.
The described Radix Astragali is 15 parts, 18 parts of the described Receptaculum Fici Pumilaes, and described Radix Actinidiae Chinensis is 30 parts, described Semen Benincasae is 15 parts.
The medicament of described medicine is tablet, capsule, granule, oral liquid, mixture or syrup.
For realizing above-mentioned second purpose, the technical scheme that the present invention takes is:
The as above application of arbitrary described medicine in preparation treatment bowelcancer medicine.
As above arbitrary described medicine suppresses the application in intestinal cancer vascular mimicry formation medicine in preparation.
It should be noted that, the Latin of described Rhizoma Curcumae is called Rhizoma Curcumae Aeruginosae; The described Receptaculum Fici Pumilae is commonly called as Fructus Fici Pumilae, is the receptacle of inflorescence (being commonly called as fruit) of Moraceae ficus species Caulis fici pumilae (Fructus Fici Pumilae) Ficus pumila L..
The advantage of medicine of the present invention is:
1, can suppress the growth of intestinal cancer tumor, there is the effect that the intestinal cancer vascular mimicry forms that suppresses;
2, made by pure Chinese medicine, there is the advantage such as have no side effect, price is low, be easy to be accepted by the patient;
3, the flavour of a drug number is few, abundant raw materials, and preparation technology is simple, and environment, without harm, is being had to good application prospect aspect treatment intestinal cancer.
The accompanying drawing explanation
Accompanying drawing 1 is respectively to organize mouse subcutaneous transplanting tumor size figure.From top to bottom successively: dosage group, medicine low dose group, chemotherapy group and scale in negative control group, medicine high dose group, medicine.
The specific embodiment
Below in conjunction with accompanying drawing, the specific embodiment provided by the invention is elaborated.
embodiment 1 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation () of medicine
6 parts of Rhizoma Curcumae, 20 parts of the Radixs Astragali, 15 parts of the Receptaculum Fici Pumilaes, 35 parts of Radix Actinidiae Chinensis, 10 parts of Semen Benincasaes, conventional method decocts.
embodiment 2 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation (two) of medicine
12 parts of Rhizoma Curcumae, 10 parts of the Radixs Astragali, 21 parts of the Receptaculum Fici Pumilaes, 25 parts of Radix Actinidiae Chinensis, 20 parts of Semen Benincasaes, conventional method decocts.
embodiment 3 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation (three) of medicine
6 parts of Rhizoma Curcumae, 10 parts of the Radixs Astragali, 21 parts of the Receptaculum Fici Pumilaes, 35 parts of Radix Actinidiae Chinensis, 10 parts of Semen Benincasaes, conventional method decocts.
embodiment 4 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation (four) of medicine
12 parts of Rhizoma Curcumae, 10 parts of the Radixs Astragali, 15 parts of the Receptaculum Fici Pumilaes, 35 parts of Radix Actinidiae Chinensis, 20 parts of Semen Benincasaes, conventional method decocts.
6 parts of Rhizoma Curcumae, 20 parts of the Radixs Astragali, 21 parts of the Receptaculum Fici Pumilaes, 35 parts of Radix Actinidiae Chinensis, 10 parts of Semen Benincasaes, conventional method decocts.
embodiment 6 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation (six) of medicine
8 parts of Rhizoma Curcumae, 17 parts of the Radixs Astragali, 16 parts of the Receptaculum Fici Pumilaes, 33 parts of Radix Actinidiae Chinensis, 13 parts of Semen Benincasaes, conventional method decocts.
embodiment 7 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation (seven) of medicine
10 parts of Rhizoma Curcumae, 13 parts of the Radixs Astragali, 20 parts of the Receptaculum Fici Pumilaes, 27 parts of Radix Actinidiae Chinensis, 17 parts of Semen Benincasaes, conventional method decocts.
embodiment 8 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation (eight) of medicine
9 parts of Rhizoma Curcumae, 15 parts of the Radixs Astragali, 18 parts of the Receptaculum Fici Pumilaes, 30 parts of Radix Actinidiae Chinensis, 15 parts of Semen Benincasaes, conventional method decocts.
It should be noted that, it is the manufacture method of Chinese medicine decoction routine that the described conventional method of embodiment 1-8 decocts, and is about to described crude drug and decocts with water into decoction.
embodiment 9 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation of medicinal tablet/capsule
Get the arbitrary described medicine of embodiment 1-8, add 9-11 times of water gaging, decoct 2-3.5 hour, leach medicine juice.Add again 9 times of water gagings, decoct 2.5 hours, leach medicine juice, merge the secondary decocting liquid, standing, the leaching supernatant, concentrated, let cool, add 3 times of amount ethanol of concentrated solution, stir precipitation and spend the night.Get supernatant, be concentrated into thick extractum; Add pharmaceutical aids, vacuum drying, pulverize and granulate, and is pressed into tablet or fills encapsulated.
embodiment 10 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation of drug particles
Get the arbitrary described medicine of embodiment 1-8, add 8-10 times of water gaging, decoct 3 hours, leach medicine juice.Add again 10 times of water gagings, decoct 2.5 hours, leach medicine juice, merge the secondary decocting liquid, standing, the leaching supernatant, concentrated, let cool, add 2 times of amount ethanol of concentrated solution, stir precipitation and spend the night.Get supernatant, be concentrated into thick extractum; Add suitable pharmaceutical aids, granulate, drying, granulate, obtain the 20g granule, packing 10g/ bag.
embodiment 11 treatment intestinal cancer and inhibition intestinal cancer vascular mimicry form the preparation of drug mixture/oral liquid/syrup
Get the arbitrary described medicine of embodiment 1-8, add 8-11 times of water gaging, decoct 3 hours, leach medicine juice.Add again 8 times of water gagings, decoct 3 hours, leach medicine juice, merge the secondary decocting liquid, standing, the leaching supernatant, concentrated, let cool, add 3.5 times of amount ethanol of concentrated solution, stir precipitation and spend the night.Get supernatant, be concentrated into thick extractum; Add suitable pharmaceutical aids, make mixture, oral liquid or syrup.
the zoopery of embodiment 12 Drug therapy intestinal cancer of the present invention
1 material
1.1 animal and tumor strain
SPF level nude mice, male, body weight 20 ± 2g, be purchased from Shanghai City Si Laike laboratory animal company limited, credit number: SCXK(Shanghai) 2003-2003; HCT116 cell (Human colorectal cancer cells), provided by Shanghai Branch of Chinese Academy of Sciences cell bank.
1.2 medicine and reagent
The Chinese medicine composition of embodiment 8 preparation, decoct to 4g(crude drug content)/solution of ml, sealing, 4 ℃ of preservations, (in medicine, the dosage group is by 5 times of normal saline dilutions, and high dose group is by 3 times of dilutions, and low dosage is by 8 times of dilutions in dilution before use.5-Fu, 250mg/10ml, be purchased from Hengrui Medicine Co., Ltd., Jiangsu Prov.; The anti-polyclonal antibody of CD34 rabbit, clone ZDP01, be purchased from U.S. R& D company; PAS solution.
2 methods
2.1 the tumor modeling of nude mice Mus subcutaneous transplantation and packet transaction
1. modeling: the CT26 cell of the trophophase of taking the logarithm, with preparing single cell suspension after trypsinization, concentration 1 * 10
6/ ml, only be inoculated in the right armpit of nude mice by 0.2ml/ subcutaneous.
2. divide into groups and process: after all going out tumor, by tumorous size, being divided at random five groups, 12 every group.Negative control (NS) group: every gavage 0.5mL normal saline; Medicine of the present invention high (YAH), in (YAM), low dosage (YAL) group: press respectively 5mg/d, 10mg/d, 15mg/d administration, every 0.5mL; Chemotherapy group: only adopt 5-Fu(25mg/kg) 0.2ml lumbar injection, 2 times/week, totally 12 days.
2.2 observe and detect
1. observation item: observe nude mice diet, defecation, active state, body weight, growth of xenografted situation every day; After experiment finishes, all animals is put to death in dislocation, weighs; Peel off the tumor body, observe the transplanted tumor size, claim the tumor weight.
2. tumour inhibiting rate: press tumour inhibiting rate=[(the average tumor weight of the average tumor weight-experimental group of negative control group)/average tumor weight of negative control group] * 100% and calculate.
2.3 CD34 and PAS double staining and VMD(vasculogenic mimicry density) measure
Method can be referring to document: Zhang Shiwu, Guo Hua, Zhang Danfang, Zhao Xiulan, Gu Yanjun, Sun Baocun. the morphological observation of Vasculogenic Mimicry in Melanoma. Chinese clinical tumor, 2005, 32 (23): on the method that 1329-1332. method of the present invention provides at document, slightly change, specific as follows: as by the Envision method, to carry out the CD34 immunohistochemical staining, optical microphotograph Microscopic observation after the DAB colour developing, after vascular endothelial cell is dyed brown color, water rinses color development stopping, with 0.5% periodic acid solution reduction, 10 min that cut into slices, current rinse 2 min and are placed in Schiff liquid, lucifuge is processed 10 min, with tap water, rinse subsequently, when cherry-red (or pink) appears in the optical microphotograph Microscopic observation, use hematoxylin understain nucleus, the acidic alcohol differentiation, ammonia returns indigo plant, Gradient elution using ethanol, dimethylbenzene is transparent, the neutral gum sealing.Optical microphotograph Microscopic observation endothelial-cell specific labelling CD34 feminine gender, extracellular matrix PAS stained positive person is for there being VM to form.Every pathological section is chosen arbitrarily 5 visual field counting VM numbers, asks its meansigma methods to be VM density in tumor.
2.4 statistical method
Application SPSS 15.0 softwares carry out statistical analysis, and data are used
± S means, carries out one factor analysis of variance LSD and compares in twos, and there is statistical significance P<0.05 for difference.
3 results
3.1 respectively organize nude mice by subcutaneous transplanted tumor size relatively
After medication 12 days, put to death all animals, weigh, peel off the tumor body, observe the transplanted tumor size, specifically see Fig. 1.As shown in Figure 1, the high, medium and low dosage group of medicine transplanted tumor size is significantly less than negative control group; Medicine high dose group transplanted tumor size is suitable with chemotherapy group, illustrates that medicine of the present invention possesses the effect that suppresses the intestinal cancer tumor growth.
3.2 respectively organize the comparison of tumor tissues VM
Each organizes tumor tissues VM formational situation in Table 1.Each comparison of organizing HCT116 cell transplanted tumor in nude mice VMD is in Table 2.From table 1 and table 2, the chemotherapy group statistical significance (P<0.05) of having compared with negative control group; The high, medium and low dosage group of the medicine statistical significance (P<0.05) of having compared with negative control group; The high, medium and low dosage group of medicine and chemotherapy group comparison not statistically significant (P > 0.05), but the medicine high dose group has the trend that suppresses better intestinal cancer VM formation.
Table 1 is respectively organized the comparison of tumor tissues VM formational situation
Table 2 respectively organize intestinal cancer HCT116 cell transplanted tumor in nude mice VMD comparison (
± S)
| Group |  |
| Negative control group | 8.938 ± 1.294 |
| The medicine low dose group | 5.875 ± 2.761 ＊ |
| Dosage group in medicine | 6.125 ± 1.553 ＊ |
| The medicine high dose group | 4.5 ± 1.102 ＊ |
| The 5-Fu group | 5.188 ± 1.193 ＊ |
With negative control group, compare: * means P<0.05.
In sum, medicine of the present invention can suppress the growth of the formation of intestinal cancer vascular mimicry and intestinal cancer tumor.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the inventive method; can also make some improvement and supplement, these improvement and supplement and also should be considered as protection scope of the present invention.
Claims (6)
1. treat intestinal cancer and suppress the medicine that the intestinal cancer vascular mimicry forms for one kind, it is characterized in that, it is to be made by the crude drug of following weight portion: Rhizoma Curcumae 6-12 part, Radix Astragali 10-20 part, Receptaculum Fici Pumilae 15-21 part, Radix Actinidiae Chinensis 25-35 part, Semen Benincasae 10-20 part.
2. medicine according to claim 1, is characterized in that, described Rhizoma Curcumae is 8-10 part, and the described Radix Astragali is 13-17 part, described Receptaculum Fici Pumilae 16-20 part, and described Radix Actinidiae Chinensis is 27-33 part, described Semen Benincasae is 13-17 part.
3. medicine according to claim 2, is characterized in that, described Rhizoma Curcumae is 9 parts, and the described Radix Astragali is 15 parts, 18 parts of the described Receptaculum Fici Pumilaes, and described Radix Actinidiae Chinensis is 30 parts, described Semen Benincasae is 15 parts.
4. medicine according to claim 1, is characterized in that, the medicament of described medicine is tablet, capsule, granule, mixture or syrup.
5. the application of the arbitrary described medicine of claim 1-4 in preparation treatment bowelcancer medicine.
6. the arbitrary described medicine of claim 1-4 suppresses the application in intestinal cancer vascular mimicry formation medicine in preparation.
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Citations (1)
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| CN101637581A (en) * | 2008-07-30 | 2010-02-03 | 张在文 | Chinese medicinal composition for treating gastric cancer |
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| CN101637581A (en) * | 2008-07-30 | 2010-02-03 | 张在文 | Chinese medicinal composition for treating gastric cancer |
Non-Patent Citations (8)
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