CN-121971445-A - Application of nelfinavir

Abstract

The application relates to the technical field of biological medicine, and particularly discloses application of nelfinavir. The nelfinavir is used for preparing a medicament for treating or preventing castration resistant prostate cancer, the medicament can induce tumor cells to generate DNA damage and activate a cell cycle blocking path mediated by cyclin so as to inhibit key biological processes such as proliferation of the tumor cells and cholesterol metabolism through specifically up-regulating the expression of DHCR7, particularly can effectively inhibit the formation and the expansion of polynuclear megacyte in castration resistant prostate cancer through up-regulating the expression of DHCR7 so as to further block malignant progression of polynuclear megacyte mediated tumors and treat drug resistance, and finally realizes the prevention and the treatment of castration resistant prostate cancer, and solves the technical bottlenecks that the conventional castration resistant prostate cancer treatment means have limited curative effect and are difficult to target and inhibit the drug resistance and the transfer capacity of polynuclear megacyte mediated.

Inventors

• Jiang Guanmin
• CHEN XIAOHUI
• QIN JINGBO
• Long Yili
• LI RONGNA
• HE HONGYING
• HUANG NAN

Assignees

• 中山大学附属第五医院

Dates

Publication Date

20260505

Application Date

20260228

Claims (10)

1. 1. The use of nelfinavir for the preparation of a medicament for the treatment or prevention of castration-resistant prostate cancer.
2. 2. The use of nelfinavir according to claim 1 wherein said medicament is for inhibiting the proliferation of human prostate cancer cells PC 3.
3. 3. The use of nelfinavir according to claim 1 wherein said medicament is for up-regulating the expression of DHCR7 in human prostate cancer cells PC 3.
4. 4. The use of nelfinavir according to claim 1 wherein said medicament is for inhibiting proliferation of multinucleated giant cells.
5. 5. The use of nelfinavir according to claim 1 wherein said medicament is for inhibiting the expression of BUB1B, cyclinB1, p-H3 and KIF18A in human prostate cancer cells PC 3.
6. 6. The use of nelfinavir according to claim 1 wherein said medicament is for inducing DNA damage in human prostate cancer cells PC 3.
7. 7. The use of nelfinavir according to claim 6 wherein said marker of DNA damage is γ -H2AX.
8. 8. The use of nelfinavir according to claim 1 wherein said medicament is for up-regulating the expression of a cell cycle arrest marker in human prostate cancer cells PC 3.
9. 9. The use of nelfinavir according to claim 8 wherein said cell cycle arrest marker is p21.
10. 10. The use of nelfinavir according to claim 1 wherein said medicament is a composition further comprising one or more pharmaceutically acceptable carriers, excipients or diluents, wherein the dosage of nelfinavir administered in said medicament is 40-120 mg/kg/day.

Description

Application of nelfinavir Technical Field The application relates to the technical field of biological medicine, in particular to application of Nelfinavir (NFV). Background Prostate cancer is the malignant tumor with the highest incidence rate and the second mortality rate in European and American men, and although the overall incidence rate in China is lower, patients are in advanced stage and are accompanied by metastasis when diagnosis is confirmed. Among them, androgen Receptor (AR) signaling pathway plays a central role in the development of prostate cancer, androgen Deprivation Therapy (ADT) being the primary therapeutic approach for advanced prostate cancer. However, most patients inevitably progress to castration-resistant prostate cancer (CRPC) after 12-18 months of treatment, exhibiting significant resistance and high metastatic capacity, and current therapeutic strategies for CRPC remain limited in efficacy. Tumor metabolic reprogramming and cell cycle regulation abnormalities are key biological features of CRPC. Among them, multinucleated giant cells (PGCC) are a special tumor cell subset present in solid tumors, originally thought to be terminal senescent cells, but recent studies indicate that PGCCs has high biological activity, and its offspring possess tumor stem, invasive metastatic capacity and significant therapeutic resistance, and are important driving factors for tumor recurrence and malignant progression. Clinical studies have also shown that PGCCs appearance is closely related to poor prognosis of prostate cancer, resistance to CRPC and rapid death. Furthermore, in hormone sensitive prostate cancer (CSPC) cells, DHCR7 is highly expressed, 7-DHC levels are low, PGCCs are very rarely produced, whereas in CRPC cells DHCR7 is significantly down-regulated with concomitant 7-DHC accumulation and PGCCs mass production. Functional experiments show that inhibiting or knocking out DHCR7 can promote PGCCs production and enhance tumor dryness and invasive metastasis capacity, while over-expressing DHCR7 can reverse the phenotype, i.e., DHCR7 under-expression is a key factor in promoting PGCCs production and malignant progression. Therefore, how to effectively intervene in the progress of prostate cancer, especially CRPC, and to target inhibition PGCCs-mediated malignant phenotype and metastasis has become a key scientific problem and clinical technical problem to be solved urgently in the field of prostate cancer at present. Disclosure of Invention Therefore, the application aims to provide an application of nelfinavir, which is used for solving the technical bottleneck that the existing CRPC treatment means have limited curative effect and are difficult to target and inhibit PGCCs-mediated drug resistance and transfer capacity. In order to achieve the technical aim, the application provides an application of nelfinavir in preparing a medicament for treating or preventing castration resistant prostate cancer. Further, the drug is used for inhibiting proliferation of human prostate cancer cells PC 3. Further, the drug is used to up-regulate DHCR7 expression in human prostate cancer cells PC 3. Further, the medicine is used for inhibiting proliferation of multinucleated giant cells. Further, the drug is used for inhibiting the expression of BUB1B, cyclinB1, p-H3 and KIF18A in human prostate cancer cells PC 3. Further, the drug is used for inducing DNA damage of human prostate cancer cells PC 3. Further, the marker of DNA damage is γ -H2AX. Further, the medicament is for upregulating the expression of cell cycle arrest markers in human prostate cancer cells PC 3. Further, the cell cycle arrest marker is p21. Further, the medicine is a composition and further comprises one or more pharmaceutically acceptable carriers, excipients or diluents, wherein the administration dosage of nelfinavir is 40-120 mg/kg/day. In summary, the application provides an application of nelfinavir in preparing a medicament for treating or preventing CRPC. The medicine can specifically up-regulate the expression of DHCR7, induce tumor cells to generate DNA damage, activate cell cycle blocking channels mediated by cyclin, inhibit proliferation of tumor cells, cholesterol metabolism and other key biological processes, and especially can effectively inhibit PGCCs in CRPC (common-point protein receptor) from forming and amplifying by up-regulating the expression of DHCR7, thereby blocking PGCCs-mediated malignant tumor progression and treating drug resistance, and finally realizing control of CRPC. Compared with the prior art, the application takes DHCR7 as a core action target, provides a brand-new CRPC control strategy from the aspects of regulating and controlling tumor metabolism reprogramming and cell cycle processes, and solves the technical problems that the existing CRPC treatment means have limited curative effect and are difficult to target and inhibit PGCCs-mediated malignant progress. Drawings In order to more clea