阅读说明：本技术 Aitc的用途 (Use of AITC ) 是由 徐迅迪 于 2020-05-26 设计创作，主要内容包括：本发明涉及医药技术领域,尤其涉及AITC的用途。本发明通过实验证明,AITC能够显著降低荷瘤小鼠的肿瘤体积、抑制肿瘤细胞的增殖,对癌症的治疗存在积极意义。因此,本发明提供了AITC在制备治疗抗肿瘤的药物中的应用,并提供了一种含有AITC的抗肿瘤药物。具体的,提供了AITC在制备治疗肝癌的药物中的应用。研究表明,对于荷瘤动物而言,AITC干预的皮下瘤体积明显小于NC组,差异有统计学意义(p＜0.01)。(The invention relates to the technical field of medicines, in particular to an application of AITC. Experiments prove that the AITC can obviously reduce the tumor volume of tumor-bearing mice and inhibit the proliferation of tumor cells, and has positive significance for treating cancers. Therefore, the invention provides the application of AITC in preparing anti-tumor medicaments and provides an anti-tumor medicament containing AITC. In particular to an application of AITC in preparing a medicament for treating liver cancer. Studies have shown that for tumor-bearing animals, the subcutaneous tumor volume of AITC intervention is significantly smaller than in the NC group, with statistical differences (p < 0.01).)

Use of AITC or an analogue thereof in the manufacture of a medicament for inhibiting tumor cell proliferation.

2. The use of claim 1, wherein said inhibiting tumor cell proliferation comprises: inhibiting the increase in the number of cells and/or inhibiting the formation of clones.

Use of AITC or an analogue thereof for the manufacture of a medicament for inhibiting tumor volume growth.

Use of AITC or an analogue thereof in the manufacture of a medicament for the treatment of a tumour.

5. The use according to any one of claims 1 to 4, wherein the tumour is a malignant tumour selected from a carcinoma, a sarcoma and/or a blastoma.

6. The use of claim 5, wherein the site of tumorigenesis comprises one or more of head and neck, brain, thyroid, esophagus, pancreas, liver, stomach, kidney, gall bladder, colon, rectum, ovary, cervix, uterus, prostate, bladder, testis.

7. The use of any one of claims 1 to 7, wherein the tumor is liver cancer.

8. The use of claim 7, wherein the liver cancer is hepatocellular carcinoma or hepatoblastoma.

9. Use according to any one of claims 1 to 8, wherein the AITC or an analogue thereof is present in an amount of 5 mg/kg-d^-1。

10. A medicament for the treatment of tumours, comprising AITC or an analogue thereof.

Technical Field

The invention relates to the technical field of medicines, in particular to an application of AITC.

Background

Cancer is a general term for malignant tumors. Characterized by uncontrolled division of abnormal cells, unlimited proliferation, invasion and destruction of surrounding normal tissues. They can be classified into carcinoma, sarcoma, blastoma, and malignant tumor according to their tissue origin. Cancer from epithelial tissue; sarcomas, which originate in adipose tissue, fibrous tissue, muscle tissue (collectively mesenchymal tissue) and lymphoid reticulum; a so-called blastoma derived from embryonic tissue; malignant tumor such as malignant schwannoma should not be used; there are also cancers specifically referred to as hematologic malignancies and are also known as leukemias. Cancer cells are also metastasized by blood and lymph fluid and can spread directly. The etiology of cancer is complex, and the main inducing factors are chemical carcinogens, special viruses, rays, hormones, free radicals and the like; genetics, diet, and mental state are important contributing factors.

Primary liver cancer ranks the top ten in malignant tumors published by the world health organization, and is the third highest in cancer lethal diseases. The number of new liver cancer cases per year exceeds 70 ten thousand, and the incidence and the mortality of the new liver cancer cases show an increasing trend. The basic principle of comprehensive treatment is inherited in liver cancer treatment, which comprises surgical operations of liver resection and liver transplantation, interventional therapy of radio frequency ablation, microwave treatment, and transcatheter arterial chemoembolization. Some targeted drugs are also used in clinic, such as sorafenib and the like. Despite the great progress made in the related diagnosis and treatment, it is still a highly lethal disease due to the very high recurrence rate and metastasis rate. The discovery of new liver cancer treatment drugs is expected to provide new approaches and means for the treatment of liver cancer.

Allyl isothiocyanate, (Allyl isothiocyanate), also known as AITC, CAS No.57-06-7, having the structural formula:

AITCs are agonists of the TRPA1 ion channel, and Transient Receptor Potential (TRP) channels are an important class of cation channel superfamily on cell membranes. TRP channels are widely distributed with different regulatory mechanisms. By sensing various internal and external stimuli, they are involved in many vital activities such as pain sensation, taste sensation, mechanical sensation, maintenance of ion homeostasis of internal and external environments of cells, regulation of muscle contraction function, cell proliferation, cell differentiation, gene transcription, cell apoptosis, cell death, and the like. TRPA1 is a member of the TRP family and is characterized by the presence of more than 14 ankyrin-binding repeats at its N-terminus, while other members contain 3 to 4 ankyrin-binding repeats. TRPA1 is distributed primarily on primary sensory neurons of the dorsal root nerve, trigeminal nerve and vagus nerve. However, the role of TRPA1 in primary hepatocellular carcinoma has not been studied.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide the use of AITC, and research shows that AITC can reduce the tumor volume of tumor-bearing mice and inhibit the proliferation of tumor cells, and has positive significance for cancer treatment.

The invention provides an application of AITC or an analogue thereof in preparing a medicament for inhibiting tumor cell proliferation.

In embodiments of the invention, said inhibiting tumor cell proliferation comprises: inhibiting the increase in the number of cells and/or inhibiting the formation of clones.

The invention also provides application of the AITC or the analogue thereof in preparing a medicament for inhibiting tumor volume increase.

The invention also provides the application of the AITC or the analogue thereof in preparing the medicine for treating the tumor.

In some embodiments, the tumor is a malignant tumor selected from a carcinoma, a sarcoma, and/or a blastoma.

In some embodiments, the site of tumorigenesis comprises one or more of head and neck, brain, thyroid, esophagus, pancreas, liver, stomach, kidney, gall bladder, colon, rectum, ovary, cervix, uterus, prostate, bladder, testis.

In some embodiments, the tumor is liver cancer.

In some embodiments, the liver cancer is hepatocellular carcinoma or hepatoblastoma.

In a specific example, Huh7 cells were used to demonstrate the therapeutic effect of AITC on hepatocellular carcinoma. The therapeutic effect of AITC on hepatoblastoma was confirmed with HepG2 cells.

In the present invention, for the cell experiments, the treatment concentration of AITC or the like is 50. mu. mol/L to 100. mu. mol/L. For animal experiments, the dose of Pyr3 or the analogue thereof is 5mg/kg d^-1. The administration mode is intraperitoneal injection, and the solvent for injection is DMSO.

The invention also provides a medicament for treating tumors, which comprises AITC or analogues thereof.

The medicine also comprises pharmaceutically acceptable auxiliary materials.

The medicine of the invention can also comprise other medicines with anti-tumor function.

In some embodiments of the present invention, the pharmaceutically acceptable excipient is one or a mixture of two or more of a flavoring agent, an osmotic pressure regulator, a filler, a lubricant, a preservative, a suspending agent, an edible pigment, a diluent, an emulsifier, a disintegrant, or a plasticizer.

Preferably, the medicament is an oral preparation or an injection. The oral preparation can be tablet, pill, oral liquid, capsule, syrup, dripping pill or granule. Preferably, the capsule is a hard capsule or a soft capsule. The tablet is oral tablet or buccal tablet. The oral tablet refers to a tablet for oral administration, and most of the tablets have the drug which is absorbed through the gastrointestinal tract to exert the effect, and some tablets have the drug which is locally exerted in the gastrointestinal tract. In some embodiments provided herein, the oral tablet is a compressed tablet, a dispersible tablet, an effervescent tablet, a chewable tablet, a coated tablet, or a sustained release tablet. The injection comprises powder injection or injection.

The invention also provides a method of treating a tumor comprising administering AITC or an analog thereof.

In the present invention, the analogue of AITC is a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer or clathrate of AITC.

The agents of the invention may be used in combination therapy, i.e. in combination with one or more other agents, wherein the combination comprises the administration of AITC together with the other agents, or sequentially. For example, the additional agent may be administered before, during, or after the administration of AITC or an analog thereof. The mode of administration may be the same or different, e.g., AITC and other agents may both be administered in injectable form, may both be administered orally, or may be administered orally, one administered by injectable form and the other.

Experiments prove that the AITC can obviously reduce the tumor volume of tumor-bearing mice and inhibit the proliferation of tumor cells, and has positive significance for treating cancers. Therefore, the invention provides the application of AITC in preparing anti-tumor medicaments and provides an anti-tumor medicament containing AITC. In particular to an application of AITC in preparing a medicament for treating liver cancer. Studies have shown that for tumor-bearing animals, the subcutaneous tumor volume of AITC intervention is significantly smaller than in the NC group, with statistical differences (p < 0.01).

Drawings

FIG. 1 shows the results of a plate cloning experiment; wherein A represents the cloning formation of each group of HepG2 cells; b shows the clone formation rate of each group of HepG2 cells; c shows the clonogenic profiles of the groups of Huh7 cells; d shows the clonality of the groups of Huh7 cells;

FIG. 2 shows the proliferative capacity of AITC for intervention in hepatoma cells, wherein A shows AITC for intervention in HepG2 cells; b shows AITC intervention Huh7 cells;

FIG. 3 shows the results of a mouse subcutaneous tumor experiment, wherein A shows the morphology of two groups of mice, the upper 4 of which are control mice and the lower four of which are AITC test mice; b shows the tumor mass in the control group (top) and the tumor mass administered with AITC intervention (bottom); c shows the curve of tumor volume change of two groups of mice with time as abscissa.

Detailed Description

The invention provides the application of AITC, and the technical personnel can appropriately improve the technological parameters for realization by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

The test materials adopted by the invention are all common commercial products and can be purchased in the market.

Female four-week-old NOD/SCID (non-obese diabetic/severe combined immunodeficiency mice) purchased from Beijing Wintoli Hua, all the mice were fed in the SPF level mouse feeding room of the experimental animal center of Xiangya II Hospital, the university of Central and south China, the ambient temperature was stabilized at 18-22 ℃, and the humidity was controlled at 50-60%. Feeding NOD/SCID mice in a plastic mouse box without toxicity or specific pathogens, feeding the mice with standard pellet feed and purified water, and keeping the circadian rhythm of the mice for 12 hours, wherein the required environment meets the requirements of national laboratory animal management and use guidelines, and all operations are approved and supervised by the animal ethics committee of Xiangya II Hospital, the university of China;

hepatoma cell lines HepG2, Huh7 were purchased from cell banks of shanghai life academy of sciences of china academy of sciences;

TRPA1 agonist AITC: allyl isothiocyanate (cat # 36682) was purchased from Sigma;

DMSO, purchased from Sigma company; v900090-500 ML; the purity is 99 percent;

vernier calipers, manufactured by Guangdong measuring tool factories, and electronic digital display of 0-150 mm;

varioskan Flash multifunctional microplate reader, Thermo.

The invention is further illustrated by the following examples: