CN-122011125-A - Polypeptide and application thereof in treatment of malignant solid tumor

Abstract

The invention discloses a polypeptide and application thereof in treating malignant solid tumors. The amino acid sequence of the polypeptide is FLFFASIISLIFYYSKKGRRSYK-NH2, and the polypeptide is named as DRP. Can be prepared by chemical synthesis. In vitro experiments show that the polypeptide shows remarkable broad-spectrum anti-tumor proliferation activity. In vivo experiments, the polypeptide showed potent growth inhibition of malignant solid tumors. In addition, cell experiments prove that the polypeptide DRP shows killing efficacy in CT26, OVCAR-8, panc-02 and other cell lines. In animal experiments, the administered mice have no toxic reaction, and have anticancer effects and anticancer application prospects.

Inventors

• WANG YING
• Yue Jianda
• TANG ZHAOYANG
• LIU ZHONGHUA
• LI DIE

Assignees

• 湖南师范大学

Dates

Publication Date

20260512

Application Date

20260402

Claims (5)

1. 1. A polypeptide for use in the treatment or prevention of a malignant solid tumor, wherein the amino acid sequence of the polypeptide is FLFFASIISLIFYYSKKGRRSYK-NH2.
2. 2. Use of the polypeptide of claim 1 in the manufacture of a medicament for the treatment or prevention of malignant solid tumors.
3. 3. The use according to claim 2, wherein the solid tumor includes, but is not limited to, lung cancer, liver cancer, breast cancer, colorectal cancer, pancreatic cancer.
4. 4. The use according to claim 2, wherein the medicament comprises a pharmaceutically acceptable salt, ester, amide, or cyclized form of the polypeptide.
5. 5. The use according to claim 2 or 3, wherein the medicament is for administration in combination with at least one other therapeutic agent selected from the group consisting of a chemotherapeutic agent, a targeted therapeutic agent, an immunomodulator, a glucocorticoid or any combination thereof.

Description

Polypeptide and application thereof in treatment of malignant solid tumor Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a polypeptide for treating or preventing malignant solid tumors. Background Malignant solid tumors such as lung cancer, liver cancer, breast cancer, colorectal cancer, pancreatic cancer and the like are one of the main causes of death in the global scope, and the clinical treatment mainly depends on comprehensive means such as surgical excision, radiotherapy, chemotherapy, targeted treatment, immunotherapy and the like. However, the existing therapies have significant limitations that surgery and radiotherapy are used as local treatment means, the effects on the metastatic advanced tumors are limited and the wounds are large, the chemotherapy lacks specificity, serious systemic side effects and multi-drug resistance problems can be caused while tumor cells are killed, the curative effect of targeted therapy is limited by specific biomarkers, the tumors are easy to generate acquired drug resistance, and the immunotherapy (such as PD-1/PD-L1 inhibitors) has breakthrough but low overall response rate and poor effect on immune 'cold tumors'. Therefore, development of novel antitumor drugs which are high-efficiency, low-toxicity and can overcome drug resistance is still an urgent clinical requirement. Polypeptide drugs are regarded as promising therapeutic approaches due to their high specificity, good tissue penetration and low immunogenicity. At present, therapeutic polypeptides mainly comprise targeting peptides, cytotoxic peptides, immunomodulatory peptides and the like, but the clinical application of the therapeutic polypeptides still faces key bottlenecks of poor in vivo stability, easy degradation by protease, insufficient tumor enrichment efficiency, single action mechanism, difficult penetration of compact tumor interstitials and the like. Based on the above, the polypeptide drugs for treating malignant solid tumors in the prior art have the common problems of short half-life in vivo, limited targeting property and permeability, easy drug resistance generation and the like. The present invention is directed to a novel polypeptide which overcomes or alleviates at least one of the above-mentioned drawbacks and provides a more stable, targeted and multiple antitumor drug candidate for the treatment of malignant solid tumors. Therefore, the exploration of novel protein polypeptides is of great importance in the treatment of malignant solid tumors. Disclosure of Invention The present invention aims to provide a novel polypeptide for treating or preventing malignant solid tumors and application thereof, so as to overcome or alleviate at least one defect in the prior art. The technical scheme of the invention is as follows: In a first aspect, the invention provides a polypeptide having the amino acid sequence FLFFASIISLIFYYSKKGRRSYK-NH2. In a second aspect, the invention provides the use of the polypeptide in the manufacture of a medicament for the treatment or prophylaxis of malignant solid tumours. In a third aspect, the present invention provides a method of treating or preventing a malignant solid tumor comprising administering to a subject in need thereof a therapeutically effective amount of the polypeptide or a pharmaceutical composition comprising the same. Further, the malignant solid tumor comprises lung cancer, liver cancer, breast cancer, colorectal cancer, pancreatic cancer and the like. Further, the medicament may be used in combination with at least one other therapeutic agent (e.g., chemotherapeutic agent, targeting agent, immunomodulator). Further, the polypeptide may be in the form of a pharmaceutically acceptable salt, ester, amide, cyclized form, or sequence variant that retains activity. The invention researches the treatment effect of DRP polypeptide on ovarian cancer, and the amino acid sequence of the DRP polypeptide is FLFFASIISLIFYYSKKGRRSYK-NH2. The in vitro experiments of the system show that the polypeptide shows broad-spectrum anti-tumor activity for the first time, and various experiments prove that the polypeptide has remarkable growth inhibition effect on malignant solid tumors, and particularly has remarkable effect in cell lines such as CT26, OVCAR-8, panc-02 and the like. Accordingly, the present invention provides a novel polypeptide for the treatment or prevention of malignant solid tumors, which is a polypeptide having the amino acid sequence FLFFASIISLIFYYSKKGRRSYK-NH2. Through animal experiments, the polypeptide shows remarkable anti-tumor activity in all mouse test models, inhibits the increase of tumor volume and reduces the weight of end-point tumor. At the same time, the body weight of each group of mice remained stable throughout the treatment period, and no significant systemic toxic response was observed. Compared with the prior art, the invention has the following remarkable a