CN110559293A - Application of pifithrin-mu in preparation of medicine for promoting skin wound healing after radiotherapy irradiation - Google Patents
Application of pifithrin-mu in preparation of medicine for promoting skin wound healing after radiotherapy irradiation Download PDFInfo
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- CN110559293A CN110559293A CN201910879939.2A CN201910879939A CN110559293A CN 110559293 A CN110559293 A CN 110559293A CN 201910879939 A CN201910879939 A CN 201910879939A CN 110559293 A CN110559293 A CN 110559293A
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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Abstract
The invention relates to the technical field of medicines, in particular to application of a p53 inhibitor pifithrin-mu in preparation of a medicine for promoting skin wound healing after radiotherapy irradiation. The invention provides a new application of a p53 inhibitor pifithrin-mu, which can recover mouse embryo fibroblast proliferation after irradiation, reduce irradiation cell apoptosis and promote the healing of skin wounds after irradiation, and has great significance for the healing of skin wounds after irradiation; the pifithrin-mu is a biological small molecule which can be artificially synthesized, so the cost is low and the pifithrin-mu can be produced in large quantities.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of a p53 inhibitor pifithrin-mu in preparing a medicine for promoting skin wound healing after radiotherapy irradiation.
Background
Radiotherapy is a therapeutic method for killing tumor cells by using the effect of Ionizing Radiation (IR), and plays an important role in the treatment of head and neck malignant tumors. According to literature statistics, about 5492200 new head and neck cancer cases are increased every year worldwide, and more than 50% of patients need to receive radiotherapy during the treatment process. Clinically, besides the therapeutic effect of radiotherapy, the frequently-induced complications are acute skin damage (mainly manifested by erythema, desquamation, hair loss, ulcer and the like) and skin wound healing disorder after surgical operation. The latter is mainly manifested by delayed healing, disunion or repeated ulceration of the local operation wound, increasing the probability of infection and tissue necrosis at the wound site, and finally turning into radiation skin ulcer.
pifithrin- μ inhibits the binding of p53 to mitochondria by decreasing the affinity of p53 to the anti-apoptotic proteins Bcl-xL and Bcl-2. pifithrin- μ is highly specific for p53 and does not protect cells from apoptosis due to overexpression of the apoptosis precursor protein Bax or the use of dexamethasone. pifithrin-. mu.s are able to rescue radiation-induced P53-mediated apoptosis of the thymocytes of naive mice and protect mice from radiation-induced fatal hematopoietic syndrome (STROM E, SATHES, KOMAROV P G, et. Small-molecule inhibitor of P53binding to mitochondria protects microorganism gamma irradiation [ J ]. Nat Chem Biol,2006.2(9):474-9. doi: 10.1038/nchemmbio 809).
At present, no report exists on the application of the p53 inhibitor pifithrin-mu in skin wound healing after irradiation.
Disclosure of Invention
The invention aims to provide a new application of a p53 inhibitor pifithrin-mu.
In a first aspect of the invention, there is provided the use of pifithrin-mu in the manufacture of a medicament for promoting healing of a skin wound following radiation treatment irradiation.
Through a large number of experimental researches, the present invention surprisingly discovers that pifithrin-mu has the effect of accelerating the recovery of the skin wound after irradiation.
The in vivo experiment proves that the pifithrin-mu can accelerate the proliferation of long-term passage cells after irradiation after blocking a p53 channel, and has no influence on the proliferation of normal cells.
In the present invention, the pifithrin-mu is a small biological molecule that can be artificially synthesized, and is commercially available from sigma or seleck.
Further, the radiotherapy irradiation of the cells is Co60Gamma ray irradiation; the total radiation dose is 10Gy, and the radiation irradiation of the mice is Co60gamma ray irradiation; the total radiation dose was 5 Gy.
In a second aspect of the invention, there is provided the use of pifithrin-mu in the preparation of a medicament or agent for promoting proliferation of dermal fibroblasts following radiation treatment irradiation.
In a third aspect of the present invention, there is provided a pharmaceutical preparation for promoting the healing of skin wounds after irradiation with radiation therapy, which comprises pifithrin- μ as an active ingredient.
Furthermore, the pharmaceutical preparation for promoting skin wound healing after radiotherapy irradiation also comprises a pharmaceutically acceptable carrier or auxiliary material.
The invention has the advantages that:
1. The invention provides a new application of p53 inhibitor pifithrin-mu, which can effectively promote the healing of skin wounds after irradiation. The method has great significance for healing of skin wounds after irradiation;
2. The pifithrin-mu is a biological small molecule which can be artificially synthesized, so the cost is low and the pifithrin-mu can be produced in large quantities.
Drawings
FIG. 1 is a photograph of the p53 inhibitor pifithrin-mu promoting proliferation of dermal fibroblasts in mice after long-term passage after irradiation. A picture shows that the content of p53 pathway downstream protein p21 is obviously reduced after the p53 inhibitor pifithrin-mu acts, which indicates that the p53 inhibitor pifithrin-mu acts well; b is a p21 protein expression quantitative result after p53 inhibitor pifithrin-mu acts; and the C picture shows that the cell proliferation rate of the 3 rd generation mouse embryo fibroblast is 1 day (24h) after the P53 inhibitor pifithrin-mu is irradiated, and the cell proliferation rate of the pifithrin-mu action group is obviously changed compared with that of a control group (P is less than 0.05).
FIG. 2. A: the wound was photographed at each time point and the results were obtained; b: and comparing the results of the histogram of the wound area at each time point.
Detailed Description
The following detailed description of the present invention will be made with reference to the accompanying drawings.
The experimental procedures, for which specific conditions are not noted in the following examples, are generally carried out under conventional conditions, or under conditions recommended by the manufacturer.
Example 1: after long-term passage of mouse fibroblasts after pifithrin-mu action irradiation, cell proliferation can be accelerated
Subjecting normally cultured mouse embryo fibroblast cells to trypsinization, suspending 3ml of culture solution in a 15ml centrifuge tube, and adding into Co60Gamma-ray irradiation is carried out under a radioactive source, the total radiation dose is 10Gy, the irradiated cells are taken back to a cell room and are laid in a culture bottle for continuous culture, passage can be continued when the cell confluence reaches more than 80%, and the irradiated cells are cultured according to the weight ratio of 1: 2, passage. When the cells were transferred to 3 rd generation, the intervention group cells (n ═ 5) were added to pifithrin- μ (concentration 10 μ M), the control group cells (n ═ 5) were set up in two groups, one group was added with the same dose of DMSO, the other group was cultured in DMEM culture solution of normal serum, cell counting was performed after 24h of culture, and the experiment was repeated 3 times. The results are shown in FIG. 1 and Table 1.
The A, B diagram in figure 1 shows that the content of p21 protein downstream of p53 pathway is obviously reduced after the p53 inhibitor pifithrin-mu acts, which indicates that the effect of the inhibitor is good, and the C diagram is the result of the cell proliferation rate of 3 rd generation mouse skin fibroblasts after 1 day (24h) after the inhibitor acts and irradiates.
TABLE 1 partial recovery of cell proliferation following pifithrin- μ intervention in mouse dermal fibroblasts
Indicates that the pifithrin-mu stem group has significant statistical difference (P <0.05) compared with the control group.
The results show that after 1 day (24h) of 3 rd generation mouse skin fibroblasts after irradiation by the p53 inhibitor pifithrin-mu, the number of cells in the p53 inhibitor pifithrin-mu action group is increased, and the difference is statistically significant compared with the DMSO action group (p < 0.05).
Example 2: after p53 gene is knocked out, the healing of the wound on the back of the mouse after irradiation can be promoted
p53-/-Female mice were purchased from southern model biotechnology, inc, and were aged 6 weeks. The experimental control group is provided with normal C57 mice, p53-/-Two groups of mice, the irradiation group is provided with a normal C57 mouse irradiation group, p53-/-Mice were irradiated in two groups for a total of four groups (n-5). In Co60Gamma-ray irradiation is carried out under a radioactive source, and the total radiation dose is 5 Gy. The following day after irradiation, artificial wounds with a diameter of 10mm were made on the backs of four groups of mice using a punch, and the wound areas were photographed and measured on the 4 th, 8 th and 12 th days, respectively. The results of the experiment are shown in FIG. 2.
Fig. 2A is the experimental results of the wound after photographing at each time point, and fig. 2B is the comparison result of the histogram of the wound area at each time point. The experimental results show that p53-/-The wound healing of the mice is faster than that of the normal irradiation group, and the wound area on the 12 th day is obviously different from that of the normal irradiation group (P)<0.001), and p53-/-no obvious statistical difference is observed between the control group and the normal control group, and the p53 gene knockout is shown to promote the healing of the wound on the back of the mouse after irradiation.
While the preferred embodiments of the present invention have been described in detail, it will be understood by those skilled in the art that the invention is not limited thereto, and that various changes and modifications may be made without departing from the spirit of the invention, and the scope of the appended claims is to be accorded the full range of equivalents.
Claims (7)
- Application of pifithrin-mu in preparation of medicines for promoting skin wound healing after radiotherapy irradiation.
- 2. Pifithrin-mu according to claim 1 in the preparation of a medicament for promoting healing of skin wounds following radiation therapy irradiationThe application of (A), wherein the radiotherapy irradiation is Co60And (4) irradiating gamma rays.
- Application of pifithrin-mu in preparation of medicine or reagent for promoting skin fibroblast proliferation after radiotherapy irradiation.
- 4. Use of pifithrin-mu according to claim 3 in the preparation of a medicament or agent for promoting proliferation of dermal fibroblasts following radiation therapy irradiation with Co60And (4) irradiating gamma rays.
- 5. A pharmaceutical preparation for promoting skin wound healing after radiotherapy irradiation contains pifithrin-mu as active ingredient.
- 6. The pharmaceutical formulation of claim 5, wherein said radiation therapy radiation is Co60And (4) irradiating gamma rays.
- 7. The pharmaceutical preparation of claim 5, wherein the pharmaceutical preparation for promoting skin wound healing after radiation treatment further comprises a pharmaceutically acceptable carrier or adjuvant.
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| CN201910879939.2A CN110559293A (en) | 2019-09-18 | 2019-09-18 | Application of pifithrin-mu in preparation of medicine for promoting skin wound healing after radiotherapy irradiation |
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| CN201910879939.2A CN110559293A (en) | 2019-09-18 | 2019-09-18 | Application of pifithrin-mu in preparation of medicine for promoting skin wound healing after radiotherapy irradiation |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170119865A1 (en) * | 2015-07-10 | 2017-05-04 | Korea University Research And Business Foundation | Method of expanding nk cell and composition for culturing |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170119865A1 (en) * | 2015-07-10 | 2017-05-04 | Korea University Research And Business Foundation | Method of expanding nk cell and composition for culturing |
Non-Patent Citations (4)
| Title |
|---|
| ACCELERATION OF CUTANEOUS WOUND HEALING BY TRANSIENT P53 INHIBIT: "Acceleration of Cutaneous Wound Healing by Transient p53 Inhibition", 《LABORATORY INVESTIGATION》 * |
| 刘静霞: "耐力训练和p53抑制剂对40周龄ICR小鼠骨骼肌自体吞噬相关基因表达的影响", 《中国优秀硕士徐学位论文全文数据库》 * |
| 孙鹏 等: "辐照后皮肤伤口愈合障碍与P53相关凋亡通路的关系", 《万方学位论文数据库》 * |
| 张静 等: "放射性皮肤损伤的机制研究进展", 《辐射研究与辐射工艺学报》 * |
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