Application of YW2301 in preparation of medicine for resisting Burkitt lymphoma

Abstract

The invention discloses an application of YW2301 in preparation of a medicine for resisting Burkitt lymphoma. CCK8 cell viability experiments are utilized to detect that the YW2301 has inhibition capability on Raji and CA46 cell proliferation; a Raji cell line is used for constructing a NON / SCID subcutaneous transplantation tumor model, the therapeutic significance of the YW2301 on Burkitt lymphoma is evaluated, and the YW2301 can effectively inhibit the tumorigenicity of Burkitt lymphoma cells and the growth speed of transplantation tumors; according to the present invention, the ALDH18A1 and c-Myc protein expression in the Burkitt lymphoma transplantation tumor tissue section is detected by using immunohistochemical staining, and the YW2301 can effectively down-regulate the ALDH18A1 and c-Myc protein expression in the Burkitt lymphoma tissue so as to further prove that the YW2301 can be used as the candidate small molecule for the Burkitt lymphoma targeted therapy;

Description

Technical Field

[0001] The invention relates to the technical field of biopharmaceuticals, and in particular to application of YW2301 in preparing a drug for resisting Burkitt's lymphoma. Background Art

[0002] Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma originating from the follicular germinal center. Due to its high malignancy and short tumor cell doubling time, patients often die within a few months if not treated in time. About 50% of BL patients are already in the progressive stage of the disease when they are discovered. Therefore, it is of great clinical significance to find new therapeutic targets and related strategies. Mutation-induced c-Myc dysregulation is one of the characteristics of BL, and its therapeutic significance is particularly prominent. However, c-Myc is considered an "undruggable" target for therapeutic intervention. Therefore, targeting the expression of c-Myc protein by targeting c-Myc upstream regulatory proteins has great prospects.

[0003] As an important subtype of the aldehyde dehydrogenase family, ALDH18A1 plays an important role in metabolic reprogramming and epigenetic regulation of tumors. Studies have shown that ALDH18A1 plays an important role in Luminal B (ER + HER2 - ) The protein expression is high in breast cancer, which is closely related to the poor prognosis of patients and is significantly positively correlated with the expression of the MYC gene. In addition, MYC can regulate the expression of ALDH18A1 in prostate cancer and Burkitt lymphoma. In our previous studies, we also found that ALDH18A1 is highly expressed in N-MYC amplified neuroblastoma cells and regulates the self-renewal of neuroblastoma.

[0004] Literature has shown that there are two c-Myc binding sites in the promoter region of the ALDH18A1 gene, suggesting that the ALDH18A1 gene may be a target gene of c-Myc. Therefore, the ALDH18A1 small molecule inhibitor YW2301 can effectively inhibit the proliferation and tumorigenicity of Burkitt lymphoma cells in vivo, and may become a potential candidate small molecule for targeted therapy. The present invention has potential clinical value for finding new therapeutic targets for Burkitt lymphoma and improving the therapeutic effect of Burkitt lymphoma patients. Summary of the invention

[0005] In view of this, the object of the present invention is to provide a use of YW2301 in the preparation of a drug for treating Burkitt's lymphoma.

[0006] In order to achieve the above object, the present invention provides the following technical solutions: 1. Use of YW2301 in the preparation of a drug for treating Burkitt's lymphoma, wherein the molecular formula of YW2301 is C 32 H 55 BrN4O, molecular structure formula is: .

[0007] In some embodiments of the present invention, YW2301 is used in the preparation of a drug for inhibiting the proliferation of Burkitt's lymphoma cells.

[0008] In some embodiments of the present invention, YW2301 is used in the preparation of a drug for inhibiting the tumorigenicity of Burkitt's lymphoma cells.

[0009] In some embodiments of the present invention, YW2301 is used in the preparation of a drug for inhibiting the expression of ALDH18A1 and c-Myc proteins in Burkitt lymphoma cell xenografts.

[0010] The beneficial effects of the present invention are as follows: the present invention discloses the use of YW2301 in the preparation of an anti-Burkitt lymphoma drug, and uses a CCK8 cell activity experiment to detect that YW2301 has an inhibitory ability on the proliferation of Raji and CA46 cells; a NON / SCID subcutaneous transplanted tumor model is constructed using a Raji cell line to evaluate the therapeutic significance of YW2301 on Burkitt lymphoma, and YW2301 can effectively inhibit the tumorigenicity of Burkitt lymphoma cells and the growth rate of the transplanted tumor; immunohistochemical staining is used to detect the expression of ALDH18A1 and c-Myc proteins in Burkitt lymphoma transplanted tumor tissue sections, and YW2301 can effectively downregulate the expression of ALDH18A1 and c-Myc proteins in Burkitt lymphoma tissues, further proving that it may be used as a candidate small molecule for targeted treatment of Burkitt lymphoma. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to make the purpose, technical solution and beneficial effects of the present invention clearer, the present invention provides the following drawings for illustration: Figure 1 To study the effect of YW2301 on the proliferation ability of Burkitt's lymphoma cells.

[0012] Figure 2 The effect of YW2301 on the tumorigenicity of Burkitt's lymphoma in vivo.

[0013] Figure 3 Effects of YW2301 on ALDH18A1 and c-Myc protein expression in Burkitt lymphoma cell xenografts. DETAILED DESCRIPTION

[0014] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0015] The Chinese name of YW2301: Hexadecylamine, molecular formula: C 32 H 55 BrN4O, manufacturer: Taosu, product number: T2188, CAS number: 553-08-2, molecular structure: Example 1: YW2301 inhibits the proliferation of Burkitt lymphoma cells The CCK8 cell activity assay was used to detect the inhibitory effect of YW2301 on the proliferation of Raji and CA46 cells. The results showed that compared with the control group, the absorbance values ​​of Raji and CA46 cells treated with YW2301 decreased significantly ( Figure 1 , AB). The above results show that the ALDH18A1 inhibitor YW2301 can significantly reduce the in vitro proliferation ability of Burkitt lymphoma cells.

[0016] Example 2: YW2301 inhibits the tumorigenicity of Burkitt's lymphoma cells in vivo A NON / SCID subcutaneous transplant tumor model was constructed using the Raji cell line to evaluate the therapeutic significance of YW2301 for Burkitt lymphoma. Doxorubicin (Dox) was used as a positive control drug and the mice were divided into four groups: Control group (normal saline group), DOX group, YW2301 group, and Low (Low concentration) group, YW2301 High (High concentration group), each group had 14 mice, 7 of which were used to observe the tumor volume, and the other 7 were used to observe the survival time of tumor-bearing mice. The Control group was intraperitoneally administered once every 2 days, and the Dox group was intraperitoneally administered once every 7 days (dose: 1 mg / kg). YW2301 Low The group received intraperitoneal administration (dose: 2 mg / kg) once every 2 days, YW2301 High The mice were intraperitoneally administered once every 2 days (dose: 6 mg / kg). According to ethical principles, when the tumor length exceeded 1.5 cm, the mice were considered dead, and the follow-up was terminated and the mice were killed. Figure 2 Shown: Compared with the control group, YW2301 High The volume of transplanted tumors in the control group was significantly reduced (the average volume of tumors in the control group was 611.54 ± 97.23 mm 3 ,YW2301High The average tumor volume in the group was 94.52 ± 48.03 mm 3 , Control group vs. YW2301 High group, n = 7, P = 6.44 × 10 -7 ), compared with the Control group, YW2301 Low The tumor volume of the YW2301 group was also reduced. Low The average tumor volume in the group was 212.77 ± 34.67 mm 3 , Control group vs. YW2301 Low group, n = 7, P = 1.10 × 10 -5 ), the tumor volume in the DOX group also decreased (the average tumor volume in the DOX group was 280.82 ± 36.99 mm 3 , Control group vs. DOX group, n = 7, P = 3.80 × 10 -5 )( Figure 2 , AB). Compared with the Control group, YW2301 High Group, YW2301 Low The weight of transplanted tumors in the control group and the DOX group was significantly reduced (the average weight of tumors in the control group was 0.42 ± 0.07 g, and the average weight of tumors in the YW2301 group was 0.42 ± 0.07 g, High The average tumor weight in the YW2301 group was 0.07 ± 0.05 g. Low The average tumor weight of the control group was 0.19 ± 0.05 g, and the average tumor volume of the DOX group was 0.18 ± 0.04 g, n = 7, Control group vs. YW2301 High group, P = 1.94 × 10 -7 ;Control group vs.YW2301 Low group, P = 2.60 × 10 -5 ; Control group vs. DOX group, P = 7.00×10 -6 )( Figure 2 , C). Kaplan-Meier analysis showed that YW2301 treatment significantly prolonged the overall survival of tumor-bearing mice ( Figure 2 , D). The above results indicate that YW2301 can effectively inhibit the tumorigenicity of Burkitt lymphoma cells and the growth rate of transplanted tumors, and may serve as a candidate small molecule for targeted therapy of Burkitt lymphoma.

[0017] Example 3: YW2301 down-regulates the expression of ALDH18A1 and c-Myc in Burkitt lymphoma cell transplanted tumor tissues Immunohistochemical staining was used to detect the expression of ALDH18A1 and c-Myc proteins in Burkitt lymphoma transplanted tumor tissue sections. The results showed that compared with the control, YW2301 High The expression of ALDH18A1 and c-Myc proteins in the tissue sections of the YW2301 group was significantly downregulated compared with the control group. Low The expression of ALDH18A1 and c-Myc proteins in the tissue sections of the PD-1 and DOX groups was also downregulated ( Figure 3 , AC). The above results indicate that YW2301 can effectively downregulate the expression of ALDH18A1 and c-Myc proteins in Burkitt lymphoma tissues, further proving that it may be a candidate small molecule for targeted therapy of Burkitt lymphoma.

[0018] The above-described embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or changes made by those skilled in the art based on the present invention are within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. The use of YW2301 in the preparation of a drug for treating Burkitt's lymphoma, characterized in that: The molecular formula of YW2301 is C 32 H 55 BrN4O, molecular structure formula is: 。 2. The use according to claim 1, characterized in that: Application of YW2301 in the preparation of a drug for inhibiting the proliferation of Burkitt's lymphoma cells.

3. The use according to claim 1, characterized in that: Application of YW2301 in the preparation of a drug for inhibiting the tumorigenicity of Burkitt's lymphoma cells.

4. The use according to claim 1, characterized in that: Use of YW2301 in the preparation of a drug for inhibiting the expression of ALDH18A1 and c-Myc proteins in Burkitt lymphoma cell xenografts.

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