A novel polypeptide and its use in endometrial cancer

Abstract

The application discloses a novel polypeptide and a composition thereof with a targeted treatment effect on endometrial cancer cells, and belongs to the biomedical field. The endometrial cancer targeting polypeptide comprises: (a) a polypeptide derived from the 1916-1934 amino acid sequence of a human ARID1A protein; and (b) a fusion protein formed by the polypeptide (a) and a transmembrane peptide element; the polypeptide or the fusion protein can specifically bind to TP53 and regulate a derived polypeptide of a TGF-beta / smad3 channel. The polypeptide disclosed by the application can effectively bind to the mutant TP53 abnormally increased in endometrial cancer cells, inhibit the phosphorylation of SMAD3 and the growth of endometrial cancer, thereby reducing the radiotherapy dose and the use concentration of a chemotherapy drug, improving the radiotherapy and chemotherapy sensitivity of the endometrial cancer cells, and having no obvious side effect on normal cells.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, and specifically relates to a novel polypeptide and its composition that have targeted therapeutic effects on endometrial cancer cells. Background Technology

[0002] Endometrial cancer (EC) is a malignant tumor that occurs in the epithelium of the uterine endometrium. In China, the incidence of endometrial cancer is 6.34 per 10,000, with a mortality rate of 2.18 per 10,000, and the incidence is increasing year by year. Conventional surgery combined with radiotherapy and chemotherapy is effective for most early-stage patients, but the treatment effect is not ideal for advanced and recurrent endometrial cancer. With the development of modern medicine, precision medicine has received increasing attention and research, and targeted therapy for endometrial cancer has provided a new treatment direction for advanced and recurrent endometrial cancer.

[0003] In recent years, research on the pathogenesis and signaling pathways of endometrioma (EC) has deepened, and some mutated genes and abnormal pathways have been confirmed to play important roles in EC treatment. According to TCGA research data, most endometrioid adenocarcinomas have mutations in ARID1A, PTEN, CTNNB1, PIK3CA, P53, and KRAS genes. These mutations lead to dysregulation of tumor suppressor gene expression, which is crucial for the occurrence and development of endometrial cancer. Correspondingly, research on targeted drugs has become a major focus in the field of endometrial cancer research.

[0004] Targeted therapies block the signaling pathways or mutated proteins essential for tumor cell growth and survival, thus inhibiting cancer cell growth. However, current EC drug treatments still face many challenges, such as drug resistance, toxicity, and poor efficacy. There is an urgent need to develop safer and more effective drugs to improve the efficacy and prognosis of EC and increase the survival rate of EC patients. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a novel polypeptide and its composition that have targeted therapeutic effects on endometrial cancer cells. The inventors discovered that in endometrial cancer cells, when the AT-rich interaction domain 1A gene (ARID1A) binds to TP53, it inhibits the transforming growth factor-β (TGF-β) signaling pathway, specifically inhibiting smad3 phosphorylation, thereby suppressing tumor cell proliferation.

[0006] To achieve the above objectives, the present invention provides the following technical solution.

[0007] This invention provides a novel targeted therapeutic polypeptide for endometrial cancer, the amino acid sequence of which is shown in SEQ ID.1;

[0008] The novel targeted therapeutic peptide for endometrial cancer is derived from the amino acid sequence of human ARID1A protein, positions 1916-1934.

[0009] This invention also provides an endometrial cancer-targeting polypeptide, comprising:

[0010] (a) The novel endometrial cancer targeted therapy polypeptide of claim 1;

[0011] (b) A fusion protein formed by a polypeptide (a) and a transmembrane peptide element;

[0012] (c) A polypeptide whose amino acid sequence corresponds to the C-terminus (1916-1934aa) of the ARID1A protein, or a fusion protein formed by the C-terminus and a transmembrane peptide element;

[0013] The polypeptide (a) or fusion protein (c) can specifically bind to TP53 and regulate the derivative polypeptides of the TGF-β / smad3 pathway.

[0014] Furthermore, it has the following uses:

[0015] (a) Use in the preparation of drugs for treating endometrial cancer;

[0016] (b) Use in the preparation of drugs to increase the radiosensitivity of endometrial cancer;

[0017] (c) Use of preparation of drugs that increase drug sensitivity in endometrial cancer.

[0018] The present invention also provides a novel targeted therapy drug for endometrial cancer, comprising the endometrial cancer targeted polypeptide as described in claim 2.

[0019] Furthermore, the drug is in any pharmacologically acceptable dosage form, preferably an injectable formulation.

[0020] Furthermore, the drug is in any pharmacologically acceptable dose.

[0021] The present invention also provides a novel radiosensitizer, comprising the endometrial cancer-targeting polypeptide as described in claim 2.

[0022] The present invention also provides a pharmaceutical composition comprising the endometrial cancer-targeting polypeptide of claim 2 and a pharmaceutically acceptable carrier.

[0023] The present invention also provides a pharmaceutical composition comprising other active ingredients having therapeutic effects on endometrial cancer, the endometrial cancer-targeting polypeptide of claim 2, and a pharmaceutically acceptable carrier.

[0024] Furthermore, the other active ingredients with therapeutic effects on endometrial cancer include, but are not limited to, cisplatin.

[0025] The beneficial effects of the present invention compared with the prior art.

[0026] (1) Through long-term and in-depth research, the inventors have discovered that the loss of ARID1A in endometrial cancer cells leads to the loss of TGF-β tumor suppressor function; ARID1A fragments derived from the C-terminal amino acid sequence of human ARID1A protein at positions 1916-1934 or containing the above sequence can specifically bind to TP53, thereby regulating the TGF-β / smad3 pathway.

[0027] (2) Screening out the smallest structural peptides that can specifically bind to TP53 and exert their effects: This invention has carried out a large number of screenings and verifications at the cellular level, and has also verified them using organoids from clinical patients, which has confirmed the regulatory effect of the core region of the peptides of this invention on the TGF-β pathway, and promoted the development of drugs for the treatment of endometrial cancer.

[0028] (3) No obvious side effects were found when the polypeptide of the present invention was administered to normal cells.

[0029] (4) By administering the polypeptide of the present invention, the radiotherapy dose and the concentration of chemotherapy drugs can be effectively reduced, and the radiotherapy and chemotherapy sensitivity of endometrial cancer cells can be enhanced. Attached Figure Description

[0030] Figure 1 This shows that the ARID1A / TGF-β axis depends on TP53; where, Figure 1 A: Shows the expression of p-SMAD3 in ARID1A knockout KLE cells compared to WT cells; Figure 1 B shows the expression of p-SMAD3 in KLE cells compared to control cells, with overexpression of the C-terminus of ARID1A. Figure 1 C shows the expression of p-SMAD3 in p53 knockout KLE cells compared to ARID1A C-terminal overexpression in WT cells.

[0031] Figure 2 The invention demonstrates that the peptide A1p (ARID1A associated peptide) inhibits KLE cell proliferation and promotes apoptosis. Figure 2 A and B show the minimal structural domain of ARID1A combined with p53; Figure 2 C shows the apoptosis of KLE cells after stimulation with A1p; Figure 2 D shows the growth rate of KLE cells after A1p stimulation; Figure 2 E represents the statistical result of growth rate; Figure 2 F shows the flow cytometry analysis of KLE cell apoptosis. Figure 2 G represents the statistical results of cell apoptosis.

[0032] Figure 3 The present invention demonstrates that the polypeptide A1p, used in conjunction with radiotherapy and chemotherapy, promotes apoptosis in KLE cells. Figure 3 A shows the apoptosis of KLE cells after radiotherapy 24 hours after the addition of the polypeptide A1p of the present invention; Figure 3 Figure B shows the apoptosis of KLE cells when the present invention's polypeptide A1P is used in combination with Cisplatin (cisplatin) and when it is used alone.

[0033] Figure 4 The present invention shows that the polypeptide A1p has an inhibitory effect on organoids of endometrial cancer derived from patients; Figure 4 A shows a successfully constructed endometrial cancer organoid; Figure 4 B: Cell viability assays showed that the polypeptide A1p of this invention promoted apoptosis in endometrial cancer organoids. Detailed Implementation

[0034] The present invention will now be described in detail with reference to specific embodiments. The following embodiments will help to understand the present invention, but these embodiments are only for illustrative purposes, and the present invention is not limited thereto. The operating methods in the embodiments are all conventional operating methods in this technical field.

[0035] Through long-term and in-depth research, the inventors discovered that the loss of ARID1A in endometrial cancer cells leads to the loss of TGF-β tumor-suppressive function. ARID1A fragments derived from or containing the C-terminal amino acid sequence 1916-1934 of the human ARID1A protein can specifically bind to p53, thereby regulating the TGF-β / smad3 pathway. This effectively reduces the tolerance of endometrial cancer cells to radiotherapy and chemotherapy drugs, significantly improves treatment efficacy, and has no obvious side effects.

[0036] Based on the above research findings, the inventors completed this invention.

[0037] The ARID1A gene is a tumor suppressor gene that encodes BRG1-associated factor 250a (BAF250a), an important subunit of the chromatin remodeling complex (SWItch / Sucrose non-ferment-able). Studies have shown that the ARID1A gene has a high mutation rate in various tumors, such as ovarian clear cell carcinoma, endometrial carcinoma, hepatocellular carcinoma, and breast cancer. These mutations or loss of expression may lead to tumorigenesis through multiple pathways.

[0038] The TGF-β signaling pathway, depending on the genes it induces, has either tumor-suppressive or tumor-promoting effects. In normal tissues, TGF-β signaling induces the expression of multiple genes, participating in cell proliferation inhibition, apoptosis induction, and autophagy activation. It also inhibits growth factors, inflammation, and angiogenesis through matrix fibroblasts, maintaining homeostasis and preventing tumor formation. During cancer development, tumor cells gradually develop tolerance to the inhibitory effects of TGF-β signaling, utilizing it to promote cell proliferation, immunosuppression, angiogenesis, epithelial-mesenchymal transition, and metastasis.

[0039] As used herein, the term "polypeptide of the invention" refers to a class of particularly useful polypeptides that are the active fragment (aa) of amino acid positions 1916-1934 of human ARID1A (referred to as the "core region"), as shown in SEQ.ID.1, or an ARID1A mutant containing the core region, or a fusion protein, derivative, or analog containing the core region.

[0040] As used herein, the terms “fragment,” “derivative,” and “analyte” refer to polypeptides that substantially retain their anti-inflammatory function or activity. The polypeptide fragments, derivatives, or analogs of the present invention may be (i) polypeptides in which one or more conserved or non-conserved amino acid residues (preferably conserved amino acid residues) are substituted, or (ii) polypeptides having substituent groups in one or more amino acid residues, or (iii) polypeptides formed by fusing the polypeptide of the present invention with another compound (such as a compound that prolongs the half-life of the polypeptide, for example, polyethylene glycol), or (iv) polypeptides formed by fusing an additional amino acid sequence to this polypeptide sequence (fusion proteins formed by fusing with a leader sequence, secretion sequence, or tag sequence such as 6His). Based on the teachings herein, these fragments, derivatives, and analogs are within the scope well known to those skilled in the art.

[0041] The preferred polypeptide of the present invention is an active fragment or protein containing amino acid sequences from positions 1916 to 1934 of the human ARID1A protein. It should be understood that the length of the active fragment containing the aforementioned core region is not limited to 19 amino acids (a polypeptide is generally composed of a core region plus a transmembrane peptide; our core region is 19 amino acids, and the transmembrane peptide is generally a well-known sequence, approximately 11 amino acids, therefore usually around 30 amino acids). It may also contain additional flanking amino acid sequences derived from the ARID1A protein. Typically, the length of this active fragment is 20-100 amino acids, preferably 21-70, and more preferably 21-40 amino acids. In this invention, the active fragment does not include the full-length ARID1A protein.

[0042] The research of this invention shows that the polypeptide of this invention can specifically bind to p53, regulate the TGF-β pathway, and thereby inhibit the growth of endometrial cancer cells. A significant advantage of the polypeptide of this invention is that it inhibits SMAD3 phosphorylation and tumor growth by binding to the abnormally increased mutant p53 in endometrial cancer cells, without significant side effects on normal cells.

[0043] Pharmaceutical compositions and therapeutic uses.

[0044] The polypeptides of this invention can be used directly for disease treatment, such as for the treatment of cancer. Other therapeutic agents can also be used simultaneously when using the polypeptides of this invention.

[0045] When the polypeptides of the present invention are administered (drugated) for therapeutic purposes, they can provide one or more of the following effects: (a) treatment of endometrial cancer; (b) binding to abnormally increased mutant P53 in endometrial cancer cells; and (c) inhibition of SMAD3 phosphorylation and tumor growth in endometrial cancer cells. Furthermore, the polypeptides of the present invention not only achieve good therapeutic effects but also have few side effects and virtually no adverse effects on normal cells.

[0046] These substances are typically formulated in a non-toxic, inert, and pharmaceutically acceptable aqueous carrier medium, with a pH usually between 5 and 8. The formulated pharmaceutical composition can be administered via conventional routes, including (but not limited to): intramuscular, intravenous, subcutaneous, intradermal, or local administration.

[0047] This invention also provides a pharmaceutical composition containing a safe and effective amount of the polypeptide of this invention and a pharmaceutically acceptable carrier or excipient. Such carriers include (but are not limited to): saline, buffer solutions, glucose, water, ethanol, and combinations thereof. The pharmaceutical formulation should be matched to the route of administration. The pharmaceutical composition of this invention can be formulated into an injectable form, for example, prepared using conventional methods with physiological saline or an aqueous solution containing glucose or other excipients. Pharmaceutical compositions such as injections and solutions are preferably manufactured under sterile conditions. The dosage of the active ingredient is a therapeutically effective amount, for example, 0.5 mg / kg body weight per day. Furthermore, the polypeptide of this invention can effectively reduce radiotherapy doses and the concentration of chemotherapeutic drugs used, and improve the radiotherapy and chemosensitivity of endometrial cancer cells.

[0048] When using the drug combination, a safe and effective amount of the polypeptide of this invention is administered to the patient, typically 0.5 mg / kg body weight. Of course, the specific dosage should also consider factors such as the route of administration, the patient's health condition, and the choice of chemotherapy drugs; these are all within the skill range of a skilled physician.

[0049] The polynucleotides encoding the polypeptides of this invention can also be used for therapeutic or preventative purposes, such as through gene therapy.

[0050] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions, such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratories Press, 1989), or as recommended by the manufacturer.

[0051] General method.

[0052] 1. A human endometrial adenocarcinoma KLE cell model was established using CRISPR / Cas9 technology with ARID1A knockout and p53 knockout.

[0053] The designed sgRNA sequence was inserted into the Cas9-puro empty vector to obtain the sgRNA recombinant plasmid. After successful sequencing, the constructed recombinant plasmid was transfected into cells. Puromycin screening was used to obtain KLE cell lines with stable knockout of ARID1A and TP53, respectively. Western blotting was used to verify the knockout efficiency.

[0054] 2. Western blotting.

[0055] Cells were lysed in RIPA lysis buffer at 4°C for 30 minutes. The lysis buffer was then centrifuged at 13,000 rpm at 4°C for 20 minutes, and the supernatant was collected. The protein concentration of the samples was determined using G250 and adjusted to the same concentration. Loading buffer was added, and after mixing, the mixture was heated at 95°C for 10 minutes to denature the proteins. The proteins were then subjected to SDS-PAGE on a polyacrylamide gel electrophoresis, transferred to a PVDF membrane, blocked with 5% skim milk at room temperature for 1 hour, and the primary antibody was diluted to the appropriate concentration with antibody dilution buffer. Hybridization was performed overnight. After washing three times with PBS, the cells were incubated with secondary antibody at room temperature for 2 hours, washed three times with PBS, and then developed using ECL.

[0056] 3. Cell culture and transfection.

[0057] Human endometrial cancer KLE cell line was cultured in DMEM medium containing 10% FBS.

[0058] Cells were seeded in 6cm culture dishes at a density of approximately 80%. 4μg of plasmid was diluted with 1mL of serum-free DMEM medium, and 8μL of transfection reagent was added and mixed thoroughly. The mixture was incubated at room temperature for 15 minutes. The resulting solution was then slowly added to the culture dishes, shaken well, and incubated at 37°C for 4–6 hours. The culture medium containing the transfection reagent was then removed, and the cells were replaced with normal culture medium for further incubation. All transfections were performed using Lipofectamine 3000 (Invitrogen).

[0059] 4. Immunoprecipitation.

[0060] Cells were harvested 24-48 hours after transfection. An appropriate amount of RIPA lysis buffer was added, and lysis was performed at 4°C for 30 minutes. The lysis buffer was then centrifuged at 13000 rpm at 4°C for 20 minutes, and the supernatant was collected. A small amount of the lysis buffer was used for Western blotting analysis. The remaining lysis buffer was incubated with 10 μL of protein G beads to remove non-specific proteins, and the mixture was gently shaken at 4°C for 1 hour. The lysis buffer was then centrifuged at 0.7×g at 4°C for 3 minutes, and the supernatant was collected. The protein concentration in the sample was determined using G250 assay. The required protein volume was calculated based on the concentration, and the volume was brought to 1 mL with PBS. Subsequently, 2 μL of the corresponding antibody was added to the sample, and the mixture was gently shaken at 4°C for 2-3 hours. Then, 20 μL of protein G beads was added, and the mixture was gently shaken at 4°C overnight. The sample was centrifuged at 0.7×g, 4℃, for 3 minutes. The supernatant was separated and added to 1 mL of pre-cooled PBS. The sample was slowly washed at 4℃ for 10 minutes, and this process was repeated 3 times. Finally, the supernatant was separated and added to 40 μL of 2×SDS loading buffer. The sample was boiled in water for 10 minutes. Western blotting analysis was then performed.

[0061] Antibodies, reagent kits, and chemicals used in the experiment.

[0062] The commercially available antibodies used in the experiments were from the following companies:

[0063] CST's mouse anti-caspase 8 antibody, anti-GFP antibody, rabbit anti-Smad3 antibody, and p-Smad3 antibody;

[0064] Sigma's mouse anti-α-tubulin antibody and rabbit anti-ARID1A antibody;

[0065] Santa Cruz's mouse anti-TP53 antibody;

[0066] eBioscience's flow cytometry apoptosis detection kit;

[0067] Unless otherwise specified, all other medicines and reagents are from Sigma.

[0068] The novel endometrial cancer targeted therapy polypeptide (A1p peptide) of this invention was directly synthesized by Shanghai Qiangyao Biotechnology Co., Ltd.

[0069] Example 1: Exploration of the regulatory mechanism of ARID1A in the TGF-β signaling pathway.

[0070] 1.1 Obtaining and culturing ARID1AKO and TP53KO KLE cell lines, see General Method 1.

[0071] 1.2 KLE ARID1AKO and KLE WT cell lines were cultured according to general method 3, seeded in 6 cm culture dishes at a density of approximately 80%, and stimulated with TGF-β (10 ng / mL). After 0.5 hours, the expression of p-SMAD3 in the cells was detected according to general method 2.

[0072] The results showed that, compared with WT cells, p-SMAD3 expression was increased in KLE cells upon ARID1A knockout (KO). Figure 1 A. This indicates that ARID1A inhibits the TGF-β signaling pathway in endometrial cancer cells.

[0073] 1.3 KLE WT cell lines were cultured and transfected according to general method 3. The experimental group was transfected with GFP-ARID1A-C plasmid, and the control group was transfected with GFP plasmid. After 24 hours, TGF-β stimulation was applied. After 0.5 hours, the expression of p-SMAD3 in the cells was detected according to general method 2.

[0074] The results showed that, compared with control cells, p-SMAD3 expression was reduced in KLE cells when ARID1A C-terminus was overexpressed. Figure 1 B. This indicates that the ARID1 AC terminus inhibits the TGF-β signaling pathway in endometrial cancer cells.

[0075] 1.4 KLE P53KO and KLE WT cell lines were cultured and transfected according to the general method 3. The experimental group was transfected with GFP-ARID1A-C plasmid, and the control group was transfected with GFP plasmid. After 24 hours, TGF-β stimulation was applied. After 0.5 hours, the expression of p-SMAD3 in the cells was detected according to the general method 2.

[0076] The results showed that in TP53 knockout KLE cells, compared with WT cells, ARID1A C-terminal overexpression did not reduce p-SMAD3 expression. Figure 1 C. This indicates that the inhibition of the TGF-β pathway by ARID1A in endometrial cancer cells must be mediated by TP53.

[0077] Example 2: The effect of the present invention's polypeptide A1p in endometrial cancer cells.

[0078] 2.1 We selected three domains at the C-terminus of ARID1A and constructed three plasmids, namely GFP-ARID1A-S1, GFP-ARID1A-S2, and GFP-ARID1A-S3 (e.g., ...). Figure 2A), then the above three plasmids, along with the Flag-TP53 plasmid and GFP plasmid with the Flag tag, were inoculated and transfected into HEK293 cell lines using general method 3. 24 hours later, the core region of ARID1A binding to TP53 was detected and analyzed according to general method 4.

[0079] The results are as follows Figure 2 As shown in Figures A and B, overexpression of TP53 with a flag tag in HEK293 cells revealed the binding of flag-tagged TP53 to the C-terminus of ARID1A in the cytoplasm, indicating that ARID1A binds to TP53 via its C-terminus. The S2 domain at the C-terminus of ARID1A is the smallest domain binding ARID1A to TP53. This demonstrates that GFP-ARID1A-S2 is the core region for ARID1A-TP53 binding.

[0080] 2.2 Human endometrial cancer KLE cell line was cultured according to general method 3, seeded in 6cm culture dishes at a density of approximately 80%, stimulated with A1p (2µM), and after 24 hours, cell apoptosis was detected and analyzed according to general method 2.

[0081] The results showed that A1p promoted apoptosis in endometrial cancer cells. Figure 2 C.

[0082] 2.3 Seed 1×10⁵ KLE cells into each 3.5 cm culture dish, with 3 dishes per replicate. Digest and count the cells in the plate every 24 hours for 4 consecutive days.

[0083] The results showed that A1p inhibited the growth of human endometrial cancer cells. Figure 2 D, Figure 2 E represents the statistical results.

[0084] 2.4 Human endometrial cancer KLE cell line was cultured according to the general method 3, stimulated with A1p, and after 24 hours, cell apoptosis was detected by flow cytometry using an Annexin V-FITC kit. For specific usage steps, please refer to the instruction manual.

[0085] The results showed that A1p promoted late-stage apoptosis in endometrial cancer cells. Figure 2 F, Figure 2 G represents the statistical result.

[0086] Example 3: The effect of the present invention's polypeptide A1p as an adjunct to radiotherapy and chemotherapy drugs.

[0087] 3.1 Human endometrial cancer KLE cell line was cultured according to general method 3, seeded in 6 cm culture dishes at a density of approximately 80%, stimulated with A1p, and radiotherapy (radiation dose 4 Gy) was performed 24 hours later. The incubation time was 4 hours, and then cell apoptosis was detected and analyzed according to general method 2.

[0088] The results showed that the A1p combined with radiotherapy group was more effective in promoting apoptosis of endometrial cancer cells and significantly increased the radiosensitivity of endometrial cancer cells compared with the radiotherapy alone or A1p alone group. Figure 3 A.

[0089] 3.2 Human endometrial cancer KLE cell line was cultured according to general method 3, seeded in 6cm culture dishes at a density of approximately 80%, and stimulated with A1p and Cisplatin. After 24 hours, cell apoptosis was detected and analyzed according to general method 2.

[0090] The results showed that the experimental group receiving A1p combined with Cisplatin (cisplatin) more effectively promoted apoptosis of endometrial cancer cells and significantly increased the drug sensitivity of endometrial cancer cells compared with the experimental groups receiving Cisplatin (cisplatin) alone or A1p alone. (See [link to study]). Figure 3 B.

[0091] Example 4: The role of A1p detection in patient-derived endometrial cancer organoids.

[0092] Five organoids from endometrial cancer were selected and treated with the same concentration of A1p. Cell viability was then measured after 72–120 hours of treatment.

[0093] The results showed that the polypeptide A1p of this invention has an inhibitory effect on endometrial cancer organoids. Figure 4 .

Claims

1. An endometrial cancer targeting polypeptide, the amino acid sequence of which is shown as SEQ ID No:

1. The endometrial cancer targeting polypeptide is derived from the amino acid sequence of 1916-1934 of human ARID1A protein.

2. An endometrial cancer targeting polypeptide, which is a fusion protein of a polypeptide with the amino acid sequence shown as SEQ ID No: 1 and a TAT element.

3. The endometrial cancer targeting polypeptide of claim 1 or 2, wherein, It has the following uses: (a) the use in the preparation of an anti-endometrial cancer drug; (b) the use in the preparation of an anti-endometrial cancer drug in combination with radiotherapy; (c) the use in the preparation of an anti-endometrial cancer drug in combination with cisplatin.

4. An endometrial cancer targeting therapeutic drug, comprising the endometrial cancer targeting polypeptide of claim 1 or 2.

5. The medicament according to claim 4, characterized in that, The drug is in any pharmaceutically acceptable dosage form.

6. The medicament according to claim 4, characterized in that, The drug is in any pharmaceutically acceptable dosage.

7. A preparation for use in combination with radiotherapy, comprising the endometrial cancer targeting polypeptide of claim 1 or 2.

8. A pharmaceutical composition, comprising the endometrial cancer targeting polypeptide of claim 1 or 2 and a pharmaceutically acceptable carrier.

9. A pharmaceutical composition, comprising other active ingredients having endometrial cancer therapeutic effects, the endometrial cancer targeting polypeptide of claim 1 or 2 and a pharmaceutically acceptable carrier.

10. The pharmaceutical composition of claim 9, wherein, The other active ingredients having endometrial cancer therapeutic effects include but are not limited to cisplatin.

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