CN-121971654-A - Application of FOXL2 in preparation of ovarian cancer differentiation promoting or treating drugs

Abstract

The invention provides an application of FOXL2 in preparation of medicines for promoting differentiation or treatment of ovarian cancer. The large sample data is utilized to develop more definite and complete-evidence-chain FOXL2 action mechanism research on the action of the FOXL2 in ovarian cancer, especially epithelial ovarian cancer, effectively verify the actions of over-expression of the FOXL2 on the inhibition of the ovarian cancer cells on the tumor formation, the promotion of differentiation, the metastasis inhibition and the like, and provide a new strategy for the treatment of the ovarian cancer.

Inventors

• LIU XIAOJUN
• XIE WEIFEN
• ZHANG XIN
• SHEN JIE

Assignees

• 中国人民解放军海军军医大学

Dates

Publication Date

20260505

Application Date

20260130

Claims (10)

1. 1. Application of a reagent for increasing the expression level of FOXL2 in preparation of medicines for treating ovarian cancer.
2. 2. The use of claim 1, wherein the ovarian cancer is epithelial ovarian cancer.
3. 3. The use according to claim 2, wherein the medicament is a medicament for promoting ovarian cancer differentiation, inhibiting ovarian cancer metastasis and recurrence or inhibiting neoplasia.
4. 4. The use according to claim 3, wherein the agent promoting ovarian cancer differentiation is selected from agents promoting the synthesis of estrogens by human ovarian cancer cells, the agent inhibiting neoplasia is selected from agents inhibiting the proliferation, migration or invasion of ovarian cancer cells, promoting apoptosis of ovarian cancer cells or inhibiting neoplasia, and the agent inhibiting metastasis and recurrence of ovarian cancer is an agent reversing epithelial-mesenchymal transition (EMT).
5. 5. The use according to claim 1 or 2, wherein the agent that increases the amount of FOXL2 expression is selected from a stability enhancing material that encapsulates exogenous FOXL2, or from a FOXL2 recombinant expression vector.
6. 6. The use according to claim 5, wherein FOXL2 has the nucleic acid sequence shown in SEQ ID No. 1.
7. 7. The method according to claim 5, wherein the stability enhancing material is selected from the group consisting of nanoparticles, PEG-modified proteins, protein microspheres, liposomes and extracellular vesicles, and the expression vector is a plasmid vector, a cosmid vector, a phage vector or a viral vector.
8. 8. Use according to claim 7, characterized in that: Wherein the viral vector is selected from adenovirus, adeno-associated virus, lentivirus, coxsackie virus, herpes simplex virus, measles virus, newcastle disease virus, parvovirus, poliovirus, reovirus, vaccinia virus or vesicular stomatitis virus.
9. 9. A pharmaceutical composition for treating ovarian cancer is characterized by comprising an active component and pharmaceutically acceptable auxiliary materials, Wherein the active ingredient is the agent for increasing the expression level of FOXL2 according to claim 5.
10. 10. The pharmaceutical composition for the treatment of ovarian cancer according to claim 9, wherein the pharmaceutical composition is used in combination with other drugs for the treatment of ovarian cancer.

Description

Application of FOXL2 in preparation of ovarian cancer differentiation promoting or treating drugs Technical Field The invention belongs to the technical field of biological detection or screening, provides application of FOXL2 in preparation of medicines for treating ovarian cancer, and particularly provides application of a reagent for increasing the expression level of FOXL2 in preparation of medicines for promoting ovarian cancer differentiation, inhibiting ovarian cancer metastasis and recurrence or inhibiting tumor formation. Background Ovarian cancer is one of the common malignant tumors of the female reproductive system, with epithelial ovarian cancer being the predominant type. Because of lack of specific clinical manifestations in early stage and limited effective screening means, patients are mostly in middle and late stages in diagnosis, and postoperative recurrence rate and drug resistance occurrence rate are high, so that overall prognosis is poor. The clinical treatment at the present stage mainly comprises surgery combined chemotherapy and molecular targeting treatment and other strategies, but the problems of limited progression-free survival time, limited treatment selection after recurrence and the like still exist in the whole. Therefore, there is a need to find novel molecular markers and therapeutic targets that are closely related to the development of ovarian cancer, useful for diagnostic typing, disease progression assessment, prognosis and therapeutic intervention, to achieve more accurate patient stratification management and to promote therapeutic benefit. The fork Box transcription factor L2 (fork Box L2, FOXL 2) belongs to a family of evolutionarily conserved transcription factors, specifically expressed in ovarian tissue. FOXL2 is a key transcription factor that regulates ovarian development and maintains ovarian function. FOXL2 is a key gene involved in sex determination at the beginning of life development, pushing gonads to differentiate toward females (i.e., ovaries), which is critical for ovarian development. Knockout of FOXL2 can result in transdifferentiation of ovarian granulosa cells of species such as mice to testis support cells, ultimately leading to a sex reversal. In adult ovaries, FOXL2 plays a role in maintaining ovarian function, is responsible for regulating granulosa cell proliferation and differentiation and directly affects steroid hormone synthesis. FOXL2 upregulates various hormones and growth factors such as follicle stimulating hormone and estrogen, thereby affecting follicle maturation and selection. FOXL2, in addition to being involved in regulating the synthesis process of steroid hormones, interacts with gonadotrophin to affect endocrine function of the ovaries. Mutations in the FOXL2 gene may lead to abnormal hormone synthesis, which in turn may trigger polycystic ovary syndrome and primary ovarian dysfunction. Furthermore, loss of FOXL2 function is also associated with the occurrence of ovarian tumors. In 90% to 95% of cases of adult ovarian granuloma (approximately 5% of ovarian malignancies), the FOXL2 gene can be found to carry characteristic mutations. In the prior art, the relation between FOXL2 and epithelial ovarian cancer and the directional conclusion of the FOXL2 serving as a diagnosis/treatment target point are inconsistent, chinese patent No. CN110628911A proposes that the FOXL2 is highly expressed in malignant ovarian tumor/epithelial ovarian tumor tissues and states that the expression level of the FOXL2 is positively correlated with the malignancy, and meanwhile, the FOXL2 expression is interfered to obviously inhibit the proliferation of ovarian cancer cells (such as SKOV 3) and promote the apoptosis of the ovarian cancer cells, so that the FOXL2 is used as a candidate target molecule for diagnosing and/or treating the epithelial ovarian cancer. However, ovarian cancer is extremely heterogeneous, and the expression characteristics and functional localization of FOXL2 in different crowd queues, different pathology types/classification/stage and different experimental systems are greatly different, which directly affects the feasibility and applicability of the FOXL2 in diagnostic stratification and therapeutic intervention strategies (such as "inhibition" or "promotion"). The prior art still lacks the correspondence relationship between the expression rule of the FOXL2 in ovarian cancers of different pathological types (especially serous ovarian cancers and the like) and the disease progression and prognosis, so the application of the FOXL2 in the ovarian cancers still needs to be explored. Applicant has previously utilized online databases to discover, based on a large number of ovarian cancer data samples, that FOXL2 is significantly less expressed in epithelial ovarian cancer than normal ovarian tissue by bioinformatic analysis and immunohistochemical staining, and that overall and progression free survival of patients with low F