Application of featinib in preparation of medicine for treating rhabdomyosarcoma

Abstract

The invention provides an application of featinib in preparation of a medicine for treating rhabdomyosarcoma, and belongs to the technical field of medicines. According to the application, a scheme for inhibiting rhabdomyosarcoma proliferation by the Fidatinib is provided for the first time, the Fidatinib remarkably inhibits growth of rhabdomyosarcoma cells and inhibits cell proliferation, a new therapeutic medication scheme is provided for treatment of rhabdomyosarcoma, and the application has a good application prospect in prevention and treatment of children rhabdomyosarcoma.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to the use of Fidatinib in preparing a medicine for treating rhabdomyosarcoma. Background Art

[0002] The JAK2 / STAT3 signaling pathway has been shown to be a core oncogenic mechanism in RMS. Sustained STAT3 phosphorylation can upregulate anti-apoptotic proteins (such as Bcl-2 and Mcl-1), pro-angiogenic factors (such as VEGF), and immunosuppressive molecules (such as PD-L1), promoting tumor proliferation and immune evasion. Fedratinib, a second-generation JAK2 inhibitor, was officially approved by the FDA in 2021 for the treatment of myelofibrosis and has demonstrated clinical efficacy. However, there is currently no evidence of its use in the treatment of rhabdomyosarcoma.

[0003] Rhabdomyosarcoma is a rare malignant tumor that develops from abnormally growing early muscle cells. It can occur anywhere in the body, but is most common in the head and neck, limbs, and genitourinary organs. Its incidence ranks third among soft tissue sarcomas, after malignant fibrous histiocytoma and liposarcoma. Therefore, the discovery of a drug that effectively inhibits the proliferation of rhabdomyosarcoma is of great significance for its treatment. Summary of the Invention

[0004] The purpose of the present invention is to develop a pharmaceutical preparation that can effectively inhibit the proliferation of rhabdomyosarcoma.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions: The present invention provides the use of Fidatinib in preparing a medicine for treating rhabdomyosarcoma.

[0006] Preferably, the rhabdomyosarcoma is childhood rhabdomyosarcoma.

[0007] Preferably, the Fidatinib is an oral drug.

[0008] Preferably, the oral dosage of Fidatinib is 40-80 mg / kg / day.

[0009] The present invention proposes for the first time a scheme for using Fidatinib to inhibit the proliferation of rhabdomyosarcoma. Fidatinib significantly inhibits the growth of rhabdomyosarcoma cells and inhibits cell proliferation, providing a new therapeutic medication regimen for the treatment of rhabdomyosarcoma and having good application prospects in the prevention and treatment of childhood rhabdomyosarcoma. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 The proliferation of two rhabdomyosarcoma cell lines after treatment with different doses of Fidatinib.

[0011] Figure 2 Effects of Fidatinib on the growth of transplanted tumors; A: Picture of subcutaneous transplanted tumors in mice; B: Comparison of mouse tumor volumes; C: Comparison of mouse tumor weights; D: Curve of mouse weight changes. DETAILED DESCRIPTION

[0012] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0013] Example 1 Dose exploration of the inhibitory effect of Fidatinib on rhabdomyosarcoma cell proliferation

[0014] Experimental Materials (1) Drug: Fedratinib, whose chemical formula is , CAS number is 936091-26-8.

[0015] (2) Cancer cells: rhabdomyosarcoma cells (RD, RH30).

[0016] (3) Cell culture medium: RPMI-1640 medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin.

[0017] Experimental groups (1) Control group: blank control (NC), rhabdomyosarcoma cells were not treated with any drugs.

[0018] (2) 0.25 μM Fidatinib group: Rhabdomyosarcoma cells were treated with 0.25 μM Fidatinib.

[0019] (3) 0.5 μM Fidatinib group: Rhabdomyosarcoma cells were treated with 0.5 μM Fidatinib.

[0020] (4) 1 μM Fidatinib group: Rhabdomyosarcoma cells were treated with 1 μM Fidatinib.

[0021] Cell proliferation inhibition assay (1) Rhabdomyosarcoma cells were cultured at 3×10 cells per well. 5 The cells were seeded in 6-well plates at a density of 100 cells / well and cultured at 37°C in 5% CO2 for 24 hours.

[0022] (2) Different concentrations of Fidatinib (0.25 μM, 0.5 μM, 1 μM, final concentration) were added and cultured for 48 hours.

[0023] (3) The cell proliferation was detected by clone formation assay.

[0024] The results are as follows Figure 1As shown in the results, Fidatinib significantly inhibited the proliferation of rhabdomyosarcoma cells in a dose-dependent manner.

[0025] Example 2 Effect of Fidatinib on the Growth of Rhabdomyosarcoma Cell Transplants and Safety Assessment

[0026] Experimental Materials (1) Drug: Fedratinib.

[0027] (2) Cancer cells: Rhabdomyosarcoma cells (RH30), injected subcutaneously into the right groin of mice.

[0028] (3) Experimental animals: BALB / c nude mice aged 4-6 weeks.

[0029] Experimental groups (1) Control group: blank control, that is, tumor-bearing nude mice were not treated with any drugs.

[0030] (2) Fidatinib group: Tumor-bearing nude mice were treated with 80 mg / kg / day of Fidatinib by oral gavage for 5 consecutive days.

[0031] Transplanted tumor experiments (1) Rhabdomyosarcoma cells were cultured at a rate of 1×10 per nude mouse. 6 The cells were inoculated subcutaneously in the groin of nude mice at a density of 10 cells / mL.

[0032] (2) When the tumor volume reaches 100-200 mm³, start drug administration.

[0033] (3) The tumor volume was measured every 2 days and the tumor growth inhibition rate was calculated; the mouse body weight was measured every 2 days.

[0034] (4) After the experiment, the nude mice were killed, the tumor tissues were taken for pathological analysis, and the weight changes of the nude mice were recorded to evaluate safety.

[0035] The results are as follows Figure 2 As shown, the application of Fidatinib significantly inhibited the growth of transplanted tumors, and the tumor volume in the treatment group was significantly smaller than that in the control group. There was no significant change in the body weight of the nude mice, indicating that the combination therapy has a good safety profile.

[0036] As can be seen from the above examples, Fidatinib has a significant inhibitory effect on the proliferation of rhabdomyosarcoma cells and its safety has been verified. (1) In terms of technical effects, the results of in vitro and in vivo experiments showed that Fidatinib has a significant inhibitory effect on the proliferation of rhabdomyosarcoma cells. In addition, the mouse model showed no significant change in the weight of nude mice, indicating that the combined treatment regimen has good safety. These data scientifically prove the significant advantages of the present invention in inhibiting tumor growth; (2) In terms of social benefits, the present invention provides a more effective treatment option for patients with rhabdomyosarcoma. In summary, the present invention has significant advantages in both technical and social benefits, and provides a new solution for the treatment of rhabdomyosarcoma.

[0037] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. Use of Fidatinib in the preparation of drugs for treating rhabdomyosarcoma.

2. The use according to claim 1, characterized in that The rhabdomyosarcoma is childhood rhabdomyosarcoma.

3. The use according to claim 1, characterized in that The Fidatinib is an oral drug.

4. The use according to claim 3, characterized in that The oral dosage of Fidatinib is 40-80 mg / kg / day.

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