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Application of cGAS inhibitor in preparation of medicine for treating T cell lymphoma

An inhibitor, lymphoma technology, applied in the field of biomedicine, can solve the problems of relapse and refractory, drug resistance of TCL patients, and no cGAS inhibitor T-cell lymphoma, and achieve the effect of inducing apoptosis and increasing sensitivity.

Active Publication Date: 2022-04-12
JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although various targeted drugs and immunotherapy provide more choices for TCL patients, some TCL patients still develop drug resistance, relapse and refractory treatment, so it is necessary to explore new treatment strategies and programs to further improve the quality of TCL patients. clinical efficacy of
However, there is no relevant research report on the use of cGAS inhibitors in the treatment of T-cell lymphoma.

Method used

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  • Application of cGAS inhibitor in preparation of medicine for treating T cell lymphoma
  • Application of cGAS inhibitor in preparation of medicine for treating T cell lymphoma
  • Application of cGAS inhibitor in preparation of medicine for treating T cell lymphoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Tumor cell proliferation inhibition experiment

[0023] Experimental Materials:

[0024] 6 TCL cell lines (purchased from ATCC): adult T-cell lymphoma MT-4 cells, lymphoblastic lymphoma MOLT4 cells, lymphoblastic lymphoma Jurkat cells, lymphoblastic lymphoma C8166 cells, mycosis fungoides H9 cells, mycosis fungoides Hut78 cells.

[0025] RU.521 was purchased from sellect company.

[0026] experimental method:

[0027] Take TCL cells in logarithmic growth phase and RU.521 (0.1uM, 1uM, 10uM) at 37°C, 5% CO 2 After co-incubating for 24h and 48h under different conditions, add 100u of TCL cells treated under different conditions into a 96-well plate, with 3 duplicate wells in each group, add 10ul of CCK8 reagent to each well under the condition of avoiding light, and incubate for 2-4h , read the absorbance value at a wavelength of 450nm, and calculate the cell proliferation activity according to the following formula:

[0028] Cell proliferation activity (rat...

Embodiment 2

[0031] Example 2 RU.521 induces apoptosis of TCL cells

[0032] TCL cells (MT-4, Hut78, Jurkat) in the logarithmic growth phase were mixed with RU.521 (1uM, 10uM) at 37°C, 5% CO 2 After co-incubating under certain conditions for 24 hours, the cell apoptosis was detected by flow cytometry. The method for detecting cell apoptosis by flow cytometry is: take 50,000-100,000 resuspended cells, centrifuge, discard the supernatant, and add Annexin Gently resuspend the cells in V-FITC binding solution (FcmacsBiotech Co., Ltd.), add 5 μl Annexin V-FITC and 10 μl propidium iodide staining solution, mix gently, and incubate at room temperature (20-25°C) in the dark for 10- 20 minutes, on the machine for flow cytometry detection. see results figure 2 .

[0033] figure 2 It is the result of flow cytometric detection of cell apoptosis of TCL cells treated with different concentrations of RU.521. It can be seen that RU.521 can induce apoptosis of TCL cells, and the level of apoptosis is...

Embodiment 3

[0034] Example 3 Proteome DIA Analysis Mining RU.521 Targets

[0035] In order to deeply study the molecular mechanism of RU.521-induced TCL cell apoptosis and explore the target of RU.521, this study intends to use DIA mode quantitative proteome analysis method to deeply study the molecular mechanism of RU.521-induced TCL cell apoptosis. Discover the target of RU.521. First, use the DDA mode of mass spectrometry to establish a TCL cell whole proteome spectral library: collect all peptides within 350-1250 Da, perform secondary fragmentation, realize the identification of proteins and peptides, and establish a spectral library. Next, DIA data collection was performed on TCL cells (Jurkat and MT-4) before and after induction with RU.521, with a fragmentation window every 20Da to achieve fragmentation of all peptide fragments within 350-1250Da, and use DIANN software to perform peptide fragmentation. Segment peak extraction, and then realize the differential analysis of the proteo...

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Abstract

The invention discloses an application of a cGAS inhibitor in preparation of a medicine for treating T cell lymphoma, the inventor finds that the cGAS inhibitor can effectively kill TCL cells within the concentration range of 0.01-10 [mu] M and shows medicine concentration dependence through experimental research, by inhibiting expression of UIMC1 (RAP80) in the TCL cells, repair of tumor cell DNA damage by the UIMC1 (RAP80) is weakened, the tumor cell DNA damage is reduced, and the T cell lymphoma treatment effect is improved. The sensitivity of cells to drugs can be improved, and TCL cell apoptosis can be induced. The invention provides a new scheme for clinical treatment of T cell lymphoma.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of cGAS inhibitors in the preparation of medicines for treating T-cell lymphoma. Background technique [0002] Lymphoma is a malignant blood disease with a high incidence rate. According to the pathological characteristics, it is divided into two categories: Hodgkin's lymphoma and non-Hodgkin's lymphoma. Among them, non-Hodgkin's lymphoma is the most common, accounting for about 80%-90% of the incidence rate. T cell lymphoma (T cell lymphoma, TCL) is a malignant tumor originating from the abnormal proliferation of T lymphocytes, which can originate in lymph nodes, extranodal tissues or skin. The incidence of TCL is low, accounting for about 10-15% of non-Hodgkin's lymphoma. TCL includes T lymphoblastic lymphoma (T-LBL), cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (Peripheral T-cell lymphoma, PTCL). T-cell lymphoma is a highly...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/4184A61P35/00
CPCY02A50/30
Inventor 金晖卢雪莹李建勇伍紫娟
Owner JIANGSU PROVINCE HOSPITAL THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIV
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