CN114259487A - Application of anwuzhisu or medicinal composition thereof in treatment of colorectal cancer - Google Patents
Application of anwuzhisu or medicinal composition thereof in treatment of colorectal cancer Download PDFInfo
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- CN114259487A CN114259487A CN202111644976.9A CN202111644976A CN114259487A CN 114259487 A CN114259487 A CN 114259487A CN 202111644976 A CN202111644976 A CN 202111644976A CN 114259487 A CN114259487 A CN 114259487A
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Abstract
The invention provides application of anwuxidin or a medicinal composition thereof in treatment of colorectal cancer, belongs to the field of colorectal cancer treatment, and solves the problems that the conventional medicament cannot effectively inhibit macrophage M2 type polarization and has an unsatisfactory chemotherapy effect. Wherein, the anwurtzitaxel can be used alone or in combination with the existing anticancer drugs such as cisplatin or 5-fluorouracil. The anwuxitin can inhibit macrophage M2 type polarization, and enhance chemotherapy sensitivity of colorectal cancer cells. The application of the anwuliptin before the cisplatin or the application of the medicine A containing the anwuliptin before the medicine B containing the cisplatin can reduce the chemotherapy sensitivity of colorectal cancer cells to the cisplatin, and the administration of the medicine containing the cisplatin can effectively improve the treatment effect of the cisplatin on colorectal cancer, thereby having good clinical medication development prospect.
Description
Technical Field
The invention relates to the field of colorectal cancer treatment, in particular to application of anwuxipin or a pharmaceutical composition thereof in colorectal cancer treatment.
Background
Colorectal cancer is one of the most common gastrointestinal cancers, accounting for 8.5% of all cancer-related deaths worldwide, second to lung, liver and stomach cancers. Chemotherapy is currently one of the major means of treatment of colorectal cancer.
Cisplatin is a first-line medicine for chemotherapy of colorectal cancer, but long-term administration can cause patients to obtain drug resistance, thereby seriously affecting the treatment effect of cancer and the life quality of patients. Tumor-associated macrophages are a major component of the tumor microenvironment. Macrophages can appear as type M2, which suppresses inflammation and promotes cancer, and type M1, which suppresses pro-inflammatory tumors. M2 macrophages are responsible for promoting tumor development and progression by promoting proliferation, migration, invasion and poor prognosis. Macrophage M2 type polarization is an important factor in promoting chemotherapy resistance of tumor cells. Inhibition of macrophage M2 type polarization is an important means for improving chemotherapy sensitivity, and the existing drugs have not ideal effect on inhibition of macrophage M2 type polarization.
The anwurtzitin (Macelin, Mace for short) is a lignanoid extracted from semen Myristicae, and has a molecular formula of C20H24O4And the molecular weight is 328.4, and the composition has anti-inflammatory, antioxidant and neuroprotective functions. At present, no research on the effect of the anwurtzitin on macrophage polarization exists, and no related medicine exists in the chemotherapy for preventing and treating the colorectal cancer of the human and the animals.
Disclosure of Invention
In view of the above analysis, the embodiment of the present invention aims to provide an application of anwuxitin or a pharmaceutical composition thereof in the treatment of colorectal cancer, so as to solve the problems that the existing drugs cannot effectively inhibit macrophage M2 type polarization, and the chemotherapy effect is not ideal.
On one hand, the embodiment of the invention provides application of the anwuweisu in preparing a medicine for treating colorectal cancer.
Further, the pentalipin inhibits macrophage M2 type polarization, so as to reduce colorectal cancer drug resistance induced by M2 type macrophages and enhance chemotherapy sensitivity of colorectal cancer cells.
Further, the anwurtzitaxel is used alone or in combination with cisplatin or 5-fluorouracil.
Further, the administration dosage of the anwurtzitaxel is 5-40 mg/kg per day and 2-4 times per week.
Further, the administration route of the anwurtzitaxel is oral.
The beneficial effects of the above technical scheme are: a new application of the anwuxidin is provided, and the anwuxidin is applied to the aspect of inhibiting macrophage M2 type polarization, and can effectively inhibit macrophage M2 type polarization, so that the chemosensitivity of colorectal cancer cells can be improved by singly using the anwuxidin, and the anwuxidin can be combined with anticancer drugs (such as cisplatin or 5-fluorouracil), so that the colorectal cancer drug resistance induced by M2 type macrophages can be reduced, and the treatment effect of the colorectal cancer cells can be effectively improved.
On the other hand, the embodiment of the invention also provides application of a medicine composition containing the anwuweisu in preparing a colorectal cancer treatment medicine, wherein the medicine composition comprises a medicine A and a medicine B; wherein,
the component of the medicine A comprises anwurtzitane;
the component of the medicine B comprises cisplatin;
the medicine A is used in a preset time period before the medicine B is taken, so that the pentacin inhibits macrophage M2 type polarization, and the chemotherapy sensitivity of colorectal cancer cells to cisplatin is reduced.
Further, the dosage of the medicine A is 5-40 mg/kg per day and 2-4 times per week.
Further, the administration route of the drug A is oral administration or intravenous injection.
Further, the medicine A or the medicine B also comprises pharmaceutically acceptable auxiliary materials or auxiliary components.
Further, the drug A is used 24 h to 1 week before the drug B is administered.
The beneficial effects of the above technical scheme are: a medicine composition for treating colorectal cancer is provided, which comprises a medicine A and a medicine B, wherein the medicine A contains anwuliptin, the medicine B contains cisplatin, and the medicine A is used in a preset time period before the medicine B is taken, so that macrophage M2 type polarization can be effectively inhibited, colorectal cancer drug resistance induced by M2 type macrophages is reduced, chemotherapy sensitivity of colorectal cancer cells is enhanced, and the treatment effect of colorectal cancer is improved.
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the disclosure, nor is it intended to be used to limit the scope of the disclosure.
Drawings
The foregoing and other objects, features and advantages of the disclosure will be apparent from the following more particular descriptions of exemplary embodiments of the disclosure as illustrated in the accompanying drawings wherein like reference numbers generally represent like parts throughout the exemplary embodiments of the disclosure.
FIG. 1 shows the Western blot assay of example 1 to examine the effect of anwurtzitin on protein expression of a marker associated with M2-type macrophages;
FIG. 2 shows the flow cytometry assay of the effect of anwurtzitin on the proportion of macrophage CD206 positive cells in example 1;
FIG. 3 shows the effect of the example 2 CCK-8 assay to detect the anti-cisplatin sensitivity of the ADP on HCT116 and SW620 cells;
FIG. 4 shows the effect of the plate cloning assay of example 2 on the number of clones of HCT116 and SW620 cells tested for anwurtzitane alone or in combination with cisplatin;
FIG. 5 shows the in vivo assay of EXAMPLE 2 to detect the inhibitory effect of a combination of anwurtzitaxel and cisplatin on the in vivo tumorigenesis of SW 620.
Reference numerals:
Control-Control group; IL-413-test group with M2 type polarization; mace-test group after ampeloptin injection; mu M-mu mol/L; relative expression; RAW 264.7-macrophage RAW 264.7; DDP-cisplatin; initity rate-inhibition rate; and # represents the true significance of the result, P <0.05 is statistical, the smaller the value of P, the greater the significance, P <0.05, P <0.01, P <0.001, # 0.05, # 0.01, P <0.01, and # 0.001.
Detailed Description
Embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.
The term "include" and variations thereof as used herein is meant to be inclusive in an open-ended manner, i.e., "including but not limited to". Unless specifically stated otherwise, the term "or" means "and/or". The term "based on" means "based at least in part on". The terms "one example embodiment" and "one embodiment" mean "at least one example embodiment". The term "another embodiment" means "at least one additional embodiment". The terms "first," "second," and the like may refer to different or the same object. Other explicit and implicit definitions are also possible below.
Example 1
The invention discloses an application of anwuzhin in preparing a colorectal cancer treatment drug. The anwuqin can be used alone or in combination with existing anticancer drugs.
A large number of researches show that the anwurtzitane has the effect of inhibiting macrophage M2 type polarization, can reduce the colorectal cancer drug resistance induced by M2 type macrophages, and can enhance the chemotherapy sensitivity of colorectal cancer cells.
Preferably, the administration dosage of the anwurtzitane is 5-40 mg/kg per day and 2-4 times per week, the administration route is oral, and the effect of inhibiting macrophage M2 type polarization is obvious.
Illustratively, the dose of anwurtzitane is 10mg/kg, 3 times per week, administered 24 h prior to administration of the anti-cancer agent.
To better illustrate the effect of anwurtzitane alone on macrophages in the treatment of colorectal cancer, two experiments are given below.
Test one: m2 type polarized in vitro experiment is carried out on IL-4/13 induced macrophage THP-1 (human source) and RAW2643.7 (mouse source), a test group is given with different concentrations of anwurtzitane (5-20 mu mol/L for 24 h), and a control group is given with the same dosage of physiological saline. The test group sequentially uses IL-4/13 (24 h) and the anwurtzitol (5-20 mu mol/L, 24 h) with different concentrations to treat THP-1 cells and RAW264.7 cells, and then detects the expression conditions of M2 type surface markers CD206, Arg1 and CD163 proteins in macrophages before and after treatment through a Western blot experiment.
The results in FIG. 1 show that the expression levels of CD206, Arg1 and CD163 proteins are significantly higher after the test group is treated with 20 ng/ml IL-4/13 for 24 h than the control group (P <0.001, which is statistically significant), indicating that 20 ng/ml IL-4/13 can induce macrophages to M2 type macrophages after being treated with 24 h. The concentration of 10 and 20 mu mol/L of anwurtzitin can obviously reduce the expression of CD206, Arg1 and CD163 proteins in M2 type macrophages. After treatment with 5. mu. mol/L of anwurtzitin, no significant changes were observed in the CD206, Arg1 and CD163 proteins in M2-type macrophages compared to control cells.
And (2) test II: CD206 expression in THP-1 cells and RAW264.7 cells before and after administration was analyzed by flow cytometry. The results in FIG. 2 show that the concentration of 10. mu. mol/L of anwurtzitin was able to inhibit the proportion of CD206 positive cells, i.e.that anwurtzitin was able to inhibit macrophage M2 polarization.
In conclusion, the expression of M2 type macrophage surface marker can be remarkably reduced by treating 10 mu mol/L and 20 mu mol/L of the anwurtzitin for 24 h, and the M2 type polarization of macrophages is inhibited, so that the colorectal cancer drug resistance induced by M2 type macrophages can be reduced, and the chemotherapy sensitivity of colorectal cancer cells can be enhanced. The single use can enhance the treatment effect of chemotherapy.
Optionally, the use of anwurtzitaxel in combination with existing anticancer drugs is also possible, e.g. in combination with cisplatin or 5-fluorouracil. Since macrophage M2 type polarization is an important factor for promoting chemotherapy resistance of tumor cells, the treatment effect of the existing anticancer drugs can be enhanced, and the skilled person can understand that.
Compared with the prior art, the embodiment provides a new application of the anwurtzitane, which is applied to the aspect of inhibiting macrophage M2 type polarization and can effectively inhibit macrophage M2 type polarization, so that the chemosensitivity of colorectal cancer cells can be improved by singly using the anwurtzitane, and the anwurtzitane can be used in combination with anticancer drugs (such as cisplatin or 5-fluorouracil), so that the drug resistance of colorectal cancer cells induced by M2 type macrophages can be reduced, and the treatment effect of the colorectal cancer cells can be effectively improved.
Example 2
In another embodiment of the invention, a pharmaceutical composition for treating colorectal cancer is disclosed, which comprises a drug A and a drug B. Wherein, the component of the medicine A comprises anwurtzitane; the component of the medicine B comprises cisplatin.
Preferably, drug a is administered within a predetermined time period prior to administration of drug B to reduce the chemotherapeutic sensitivity of colorectal cancer cells to cisplatin.
Researches show that the treatment effect of the combined use mode of the anwuxidin and the cisplatin on the colorectal cancer can be obviously enhanced.
Preferably, the preset time period can be set to different people and different animals according to actual needs and experiments, and the preset time period is set to be different, such as one day (24 h) -one week.
Preferably, the dosage of the drug A is 5-40 mg/kg of the administration dosage of the anwurtzitaxel, and 2-4 times per week. The administration route is oral or intravenous injection.
To further illustrate the therapeutic effect of the pharmaceutical composition on colorectal cancer cells in the treatment of colorectal cancer, a set of experiments was performed below.
And (3) test III: the test group co-cultures two large intestine cancer cell lines of HCT116 and SW620 and M2 type macrophages or M2 type macrophages treated by the anwurtziten, and then treats the cells for 24 hours by using 0-80 mu mol/L cis-platinum (medicine B); the control group was treated with only 0-80. mu. mol/L cisplatin (drug B) for 24 h. The results in fig. 3 show that the activity of colon cancer cells co-cultured with M2-type macrophages is significantly higher than that of the control group, and the activity of colon cancer cells in the co-cultured group can be significantly inhibited by the pentalipin (drug a).
Preferably, the medicament A or the medicament B can also comprise pharmaceutically acceptable auxiliary materials or auxiliary components. The adjuvant or auxiliary ingredient should not diminish the therapeutic effect of drug a or drug B, such as vitamins and the like.
Illustratively, in vitro experiments, the dosage of drug A should be up to a dosage of 10 μmol/L of anwurtzitaxel administered for 24 h in oral form.
In order to further illustrate the therapeutic effect of the pharmaceutical composition added with the auxiliary materials on colorectal cancer cells in colorectal cancer treatment, two groups of experiments are performed below.
And (4) testing: HCT116 and SW620 cells were co-cultured with M2-type macrophages or M2-type macrophages treated with drug A and then treated with 20. mu. mol/L of drug B for 24 h. The results of the plate cloning test of fig. 4 further show that drug a in combination with drug B significantly inhibited the number of colon cancer cell clones co-cultured with M2-type macrophages.
And (5) testing: in vivo experiments, SW620 cells or the mixture (1: 1) of the SW620 cells and RAW264.7 cells are injected into the back side of a nude mouse to establish a nude mouse tumor-bearing model. One week after injection, cisplatin (4 mg/kg, once a week) drug a and/or 200uL of anwurtzitane (10 mg/kg, thrice a week) drug B were administered via tail vein injection and the control group was given an equivalent amount of physiological saline (1 time daily), in groups. After 28 days, nude mice were sacrificed and tumor tissue was collected. The results in fig. 5 show that drug a in combination with drug B can significantly reduce tumor size and weight.
The test results show that the pharmaceutical composition can reduce the sensitivity of colon cancer cells to cisplatin, the anwuxidin can improve the sensitivity of the cisplatin by inhibiting macrophage M2 polarization, the problem of colorectal cancer drug resistance induced by M2 type macrophages is solved, and the pharmaceutical composition has good clinical medication development prospects.
Compared with the prior art, the embodiment provides a pharmaceutical composition for treating colorectal cancer, which comprises a drug A and a drug B, wherein the drug A contains anwuliptin, the drug B contains cisplatin, and the drug A is used in a preset time period before the drug B is taken, so that macrophage M2 type polarization can be effectively inhibited, colorectal cancer drug resistance induced by M2 type macrophages is reduced, chemotherapy sensitivity of colorectal cancer cells is enhanced, and treatment effect of colorectal cancer is improved.
Having described embodiments of the present disclosure, the foregoing description is intended to be exemplary, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles of the embodiments, the practical application, or improvements made to the prior art, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.
Claims (10)
1. Application of anwuzhisu in preparing medicine for treating carcinoma of large intestine is provided.
2. The use of anwurtzitane in the preparation of a medicament for the treatment of colorectal cancer according to claim 1, wherein the anwurtzitane inhibits macrophage M2 type polarization to reduce M2 type macrophage-induced colorectal cancer resistance and to enhance chemotherapy sensitivity of colorectal cancer cells.
3. Use of anwurtzitaxenic acid according to claim 1 or 2, wherein the anwurtzitaxenic acid is used alone or in combination with cisplatin or 5-fluorouracil for the preparation of a medicament for the treatment of colorectal cancer.
4. The use of anwurtzitane in claim 3, in the preparation of a medicament for the treatment of colorectal cancer, wherein the administration dose of anwurtzitane is 5-40 mg/kg per day, 2-4 times per week.
5. The use of anwurtzitane in the preparation of a medicament for the treatment of colorectal cancer according to claim 4, wherein the administration route of anwurtzitane is oral.
6. The application of a medicinal composition containing the anwurtzitane derivative in preparing medicaments for treating the colorectal cancer is characterized in that the medicinal composition comprises a medicament A and a medicament B; wherein,
the component of the medicine A comprises anwurtzitane;
the component of the medicine B comprises cisplatin;
the medicine A is used in a preset time period before the medicine B is taken, so that the pentacin inhibits macrophage M2 type polarization, and the chemotherapy sensitivity of colorectal cancer cells to cisplatin is reduced.
7. The use of the pharmaceutical composition according to claim 6, wherein the amount of the drug A is 5-40 mg/kg of the anwurtzitaxel per day, 2-4 times per week.
8. Use of the pharmaceutical combination according to claim 6 or 7 for the preparation of a medicament for the treatment of colorectal cancer, wherein the route of administration of the medicament A is oral or intravenous.
9. The use of the pharmaceutical composition according to claim 8 for the preparation of a medicament for the treatment of colorectal cancer, wherein the medicament A or the medicament B further comprises pharmaceutically acceptable excipients or auxiliary components.
10. The use of the pharmaceutical composition according to claim 9 for the preparation of a medicament for the treatment of colorectal cancer, wherein the medicament a is administered 24 h to 1 week before the administration of the medicament B.
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| CN113527368A (en) * | 2021-08-12 | 2021-10-22 | 中国科学技术大学 | Preparation method and application of compound and anticancer drug |
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| LEE, YEONG-GEUN等: "Anwulignan from the fruits of Schisandra chinensis and its cytotoxicity against human cancer cell lines", PHARMACOGNOSY MAGAZINE, vol. 16, no. 72, pages 695 - 599 * |
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