Use of srsf3 inhibitors in the preparation of a product for the treatment and / or prevention of acute lymphoblastic leukemia

Abstract

The application discloses application of an SRSF3 inhibitor in preparation of a product for treating and / or preventing acute lymphoblastic leukemia (ALL). The application is based on a protein structure of SRSF3, a molecular docking model of a drug and SRSF3 is simulated by using an artificial intelligence algorithm, drug molecules most likely to be combined with SRSF3 are screened from more than 2,000 drugs approved by the FDA, and the screened drugs are functionally verified through a cell experiment, and finally, the SRSF3 inhibitor capable of being used for treating and / or preventing ALL is obtained.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to the use of SRSF3 inhibitors in the preparation of products for treating and / or preventing acute lymphoblastic leukemia. Background Art

[0002] The full name of the SRSF3 gene is Serine / Arginine-Rich Splicing Factor 3, which is located in the human chromosome 6p21.3 region. The protein encoded by the SRSF3 gene is a splicing factor that plays a key role in the RNA splicing process after gene transcription. Studies have reported that SRSF3 expression is abnormally upregulated in a variety of solid tumors, such as breast cancer and lung cancer. High expression of SRSF3 can promote the proliferation, migration and invasion of cancer cells. It can regulate the splicing of some tumor-related genes to produce mRNA isoforms that are conducive to tumor growth and metastasis. SRSF3 may also play a role in some neurodegenerative diseases. Although the specific mechanism is not yet fully understood, studies have found that it may be related to abnormal RNA metabolism, which in turn affects the normal function and survival of neurons.

[0003] Currently, research on small-molecule inhibitors targeting SRSF3 is very limited. Although studies have reported that high concentrations of theophylline can downregulate SRSF3 expression in cervical and breast cancer, and that high concentrations of amiodarone can also lead to SRSF3 degradation via the NMD pathway in HeLa cells, these concentrations are far higher than the physiological drug concentrations used in clinical treatment and therefore cannot be directly applied clinically. Therefore, the search for new SRSF3 inhibitors remains a pressing issue. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention proposes the use of SRSF3 inhibitors in the preparation of products for the treatment and / or prevention of acute lymphoblastic leukemia (ALL). Based on the protein structure of SRSF3, the present invention uses artificial intelligence algorithms to simulate the molecular docking model of drugs and SRSF3, screens out drug molecules most likely to bind to SRSF3 from more than 2,000 FDA-approved drugs, and functionally verifies the screened drugs through cell experiments, ultimately obtaining SRSF3 inhibitors that can be used to treat and / or prevent ALL.

[0005] The present invention also provides a pharmaceutical composition.

[0006] The present invention also provides an application of the SRSF3 inhibitor.

[0007] The present invention also provides the use of any one of drospirenone, methylprogesterone and conivaptan.

[0008] According to a first aspect of the present invention, a use of a SRSF3 inhibitor in the preparation of a product for treating and / or preventing acute lymphoblastic leukemia is proposed.

[0009] In some embodiments of the present invention, the SRSF3 inhibitor includes at least one of drospirenone, methylprogesterone, conivaptan, and pharmaceutically acceptable salts thereof.

[0010] In some embodiments of the present invention, the amount of drospirenone is 18-50 μM.

[0011] In some embodiments of the present invention, the amount of drospirenone is 20-40 μM.

[0012] In some embodiments of the present invention, the dosage of methylprogesterone is 20-50 μM.

[0013] In some embodiments of the present invention, the dosage of methylprogesterone is 20-40 μM.

[0014] In some embodiments of the present invention, the amount of conivaptan is 10-50 μM.

[0015] In some embodiments of the present invention, the amount of conivaptan is 20-40 μM.

[0016] According to a second aspect of the present invention, a pharmaceutical composition is provided, comprising a SRSF3 inhibitor.

[0017] In some embodiments of the present invention, the SRSF3 inhibitor includes at least one of drospirenone, methylprogesterone, conivaptan, and pharmaceutically acceptable salts thereof.

[0018] In some embodiments of the present invention, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0019] In some embodiments of the present invention, the pharmaceutically acceptable excipients include at least one of a binder, a disintegrant, a lubricant, a coating agent, a suspending agent, a thickening agent, and a surfactant.

[0020] In some embodiments of the present invention, the binder is selected from at least one of gum arabic, gelatin, dextrin, hydroxypropyl cellulose, methyl cellulose or polyvinyl pyrrolidone.

[0021] In some embodiments of the present invention, the disintegrant is selected from at least one of corn starch, potato starch, cross-linked polyvinyl pyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium or alginic acid.

[0022] In some embodiments of the present invention, the lubricant is selected from at least one of micropowder silica gel, magnesium stearate, calcium stearate, stearic acid, talc or anhydrous silica gel.

[0023] In some embodiments of the present invention, the coating agent includes at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, cellulose acetate phthalate, polyvinyl phthalate, ethyl cellulose, and cellulose acetate.

[0024] In some embodiments of the present invention, the suspending agent includes at least one of gum arabic, gelatin, methyl cellulose, sodium carboxymethyl cellulose, hydroxymethyl cellulose or aluminum stearate gel.

[0025] In some embodiments of the present invention, the surfactant is selected from at least one of lecithin, sorbitan monooleate, or glyceryl monostearate.

[0026] In some embodiments of the present invention, the administration of the drug includes but is not limited to oral, enteral, subcutaneous, intramuscular, intravenous, nasal, transdermal, subconjunctival, intraocular, orbital, retro-ocular, retinal, choroidal, and intrathecal injection.

[0027] In some embodiments of the present invention, the dosage form of the drug includes but is not limited to tablets, capsules, pills, injections, inhalants, lozenges, suppositories, emulsions, microemulsions, submicroemulsions, nanoparticles, gels, powders, suspensoids, creams, jellies, and sprays.

[0028] According to a third aspect of the present invention, the use of a SRSF3 inhibitor in the preparation of an acute lymphoblastic leukemia cell line proliferation inhibitor, an acute lymphoblastic leukemia cell line apoptosis promoter, or an acute lymphoblastic leukemia cell line cell cycle arrester is proposed.

[0029] In some embodiments of the present invention, the acute lymphoblastic leukemia cell line is a cell line that induces acute lymphoblastic leukemia.

[0030] In some embodiments of the present invention, the acute lymphoblastic leukemia is B-lineage acute lymphoblastic leukemia (B-ALL).

[0031] In some embodiments of the present invention, the chronic lymphocytic leukemia cell line includes MNAML-6 cells and / or HAL-01 cells.

[0032] In some embodiments of the present invention, the SRSF3 inhibitor includes at least one of drospirenone, methylprogesterone, conivaptan, and pharmaceutically acceptable salts thereof.

[0033] In some embodiments of the present invention, the half-maximal inhibitory concentration of drospirenone when treating NALM-6 cells is 38-45 μM.

[0034] In some embodiments of the present invention, the half-maximal inhibitory concentration of drospirenone when treating HAL-01 cells is 15-20 μM.

[0035] In some embodiments of the present invention, the methylprogesterone has a half-maximal inhibitory concentration of 25 to 30 μM when treating NALM-6 cells.

[0036] In some embodiments of the present invention, the half-maximal inhibitory concentration of methylprogesterone when treating HAL-01 cells is 20-30 μM.

[0037] In some embodiments of the present invention, the half-maximal inhibitory concentration of conivaptan when treating NALM-6 cells is 10-15 μM.

[0038] In some embodiments of the present invention, the half-maximal inhibitory concentration of conivaptan when treating HAL-01 cells is 15-25 μM.

[0039] According to a fourth aspect of the present invention, the use of any one of drospirenone, methylprogesterone and conivaptan in the preparation of an SRSF3 inhibitor is proposed.

[0040] The present invention has at least the following beneficial effects:

[0041] The present invention proposes the use of SRSF3 inhibitors in the preparation of products for the treatment and / or prevention of acute lymphoblastic leukemia. Based on the protein structure of SRSF3, the present invention uses an artificial intelligence algorithm to simulate the molecular docking model of drugs and SRSF3, screens out drug molecules most likely to bind to SRSF3 from more than 2,000 FDA-approved drugs, and functionally verifies the screened drugs through cell experiments. Ultimately, three SRSF3 inhibitors that can be used to treat and / or prevent ALL are obtained. The present invention provides more drug options for the clinical treatment of ALL. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The present invention will be further described below with reference to the accompanying drawings and embodiments, in which:

[0043] Figure 1 This is a cell viability curve diagram of ALL cells treated with different SRSF3 inhibitors in Example 2 of the present invention;

[0044] Figure 2Graph showing the results of the inhibitory effect of drospirenone on ALL cells in Example 3 of the present invention; A represents the proliferation of ALL cells treated with drospirenone within 72 hours, and B represents the colony formation of ALL cells on the 10th day after treatment with drospirenone; the scale bar is 100 μm; “**” represents p less than 0.01, and “***” represents p less than 0.001;

[0045] Figure 3 Figure 3 shows the results of cell cycle detection of ALL cells after 48 hours of drospirenone treatment in Example 3 of the present invention; wherein, "**" represents p less than 0.01, and "***" represents p less than 0.001;

[0046] Figure 4 Graph showing the inhibitory effect of methylprogesterone on ALL cells in Example 4 of the present invention; A represents the proliferation of ALL cells treated with methylprogesterone within 72 hours, and B represents the colony formation of ALL cells on the 10th day after treatment with methylprogesterone; scale bar: 100 μm; "**" represents p less than 0.01, and "***" represents p less than 0.001;

[0047] Figure 5 Figure 4 shows the results of cell cycle detection in ALL cells after 48 hours of treatment with methylprogesterone in Example 4 of the present invention; wherein, "***" indicates that p is less than 0.001;

[0048] Figure 6 Graph showing the results of the test of the inhibitory effect of conivaptan on ALL cells in Example 5 of the present invention; wherein A represents the proliferation of ALL cells treated with conivaptan within 72 hours, and B represents the colony formation of ALL cells on the 10th day after treatment with conivaptan; the scale bar is 100 μm; "***" indicates p is less than 0.001;

[0049] Figure 7 The results of cell cycle detection in ALL cells after 48 hours of conivaptan treatment in Example 5 of the present invention are shown in FIG. 5 ; “**” represents p less than 0.01, and “***” represents p less than 0.001. DETAILED DESCRIPTION

[0050] The following will clearly and completely describe the concept and technical effects of the present invention in conjunction with the embodiments to fully understand the purpose, features and effects of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0051] All drugs used in the following examples were purchased from Shanghai Taoshu Biotechnology Co., Ltd.

[0052] Example 1 Screening of SRSF3 inhibitors

[0053] This example uses an intelligent drug screening model based on a large pre-trained model of compounds and proteins and a molecular docking model to screen for SRSF3 inhibitors, thereby screening for drug molecules with potential as SRSF3 inhibitors. The screening method is as follows:

[0054] The amino acid sequence and 3D protein structure data of the target protein SRSF3 (UniProt ID: P84103) were obtained from the UniProt database, and the molecular structures of 2,975 compounds from the FDA-approved ZINC drug library were obtained; the region where the protein and compound were docked was determined, and the probability of interaction between the molecules in the ZINC drug library and SRSF3 was calculated using an artificial intelligence model. The top 100 molecules were then further docked and scored using a molecular docking model. Finally, based on the docking scores and docking conformations, the top 10 drug molecules most likely to bind to SRSF3 were screened, namely drospirenone, eplerenone, triamcinolone, adapalene, conivaptan, idarubicin, desonide, palbociclib, testosterone, and methylprogesterone. Among them, idarubicin is an anthracycline cell cycle non-specific anti-tumor drug that has been used in the clinical treatment of B-ALL, which indirectly verifies the effectiveness of the artificial intelligence virtual screening model of this embodiment.

[0055] Example 2 IC50 of different SRSF3 inhibitors in treating ALL cells

[0056] This example tested the half-maximal inhibitory concentration (IC50) of different SRSF3 inhibitors in treating ALL cell lines (NAML-6 cells and HAL-01 cells). The specific test methods and results are as follows:

[0057] 1) Count the number of NAML-6 cells and HAL-01 cells and resuspend them in RPMI 1640 medium containing 10% FBS to a concentration of 1×10 5 Cell suspension of 100 cells / mL;

[0058] 2) Set a drug concentration gradient of 0 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM, 50 μM, and 100 μM, and add drospirenone (Cat. No. T1541), eplerenone (Cat. No. T0083), triamcinolone (Cat. No. T0798), adapalene (T10246), conivaptan (Cat. No. T6453), desonide (Cat. No. T1168), palbociclib (Cat. No. T1785), and methylprogesterone (Cat. No. T16338) to the cell suspension according to the above concentration gradient; after thorough mixing, transfer to a 96-well plate for culture, add 100 μL of cell suspension to each well, and make four replicates for each drug concentration and blank control (cell-free culture medium). Transfer to a 37°C incubator and treat for 48 hours;

[0059] 3) Add 10 μL of CCK8 to each well, gently shake the plate, and place in a 37°C incubator for 2 hours;

[0060] 4) The absorbance at a wavelength of 480 nm was detected by a microplate reader, and the corresponding cell viability was calculated based on the absorbance. The calculation formula is as follows: cell viability (%) = [OD (drug group) - OD (blank control)] / [OD (drug concentration 0 group) - OD (blank control)] × 100%; a curve of drug concentration and cell viability was drawn based on the cell viability at different drug concentration gradients, and the data were fitted using nonlinear regression analysis to calculate IC50. The results are shown in the figure. Figure 1 shown.

[0061] Depend on Figure 1 It can be seen that:

[0062] Adapalene has a 50% inhibitory effect on NAML-6 cells at a concentration of 1.964 μM; and has a 50% inhibitory effect on HAL-01 cells at a concentration of 0.9064 μM.

[0063] Palbociclib has a 50% inhibitory effect on NAML-6 cells at a concentration of 1.251 μM; and has a 50% inhibitory effect on HAL-01 cells at a concentration of 0.4318 μM.

[0064] Drospirenone has a half-maximal inhibitory effect on NAML-6 cells at a concentration of 40.80 μM; and has a half-maximal inhibitory effect on HAL-01 cells at a concentration of 18.89 μM.

[0065] Methylprogesterone has a half-inhibitory effect on NAML-6 cells at a concentration of 30.05 μM; and has a half-inhibitory effect on HAL-01 cells at a concentration of 25.01 μM.

[0066] Conivaptan has a 50% inhibitory effect on NAML-6 cells at a concentration of 12.72 μM; and has a 50% inhibitory effect on HAL-01 cells at a concentration of 19.58 μM.

[0067] Eplerenone has a half-maximal inhibitory effect on NAML-6 cells at a concentration of 97.17 μM; and has a half-maximal inhibitory effect on HAL-01 cells at a concentration of 107.7 μM.

[0068] Desonide has a half-maximal inhibitory effect on NAML-6 cells at a concentration of 105.6 μM; and has a half-maximal inhibitory effect on HAL-01 cells at a concentration of 1785 μM.

[0069] Triamcinolone has a 50% inhibitory effect on NAML-6 cells at a concentration of 114.7 μM; and has a 50% inhibitory effect on HAL-01 cells at a concentration of 8889 μM.

[0070] The above results indicate that SRSF3 inhibitors can effectively inhibit the cell viability of ALL cell lines in vitro and have therapeutic potential for ALL.

[0071] Example 3 Inhibitory effect of drospirenone on ALL cell lines

[0072] This example detects the proliferation curve, clonogenicity, and cell cycle of ALL cell lines (NAML-6 cells and HAL-01 cells) after treatment with drospirenone. The specific detection methods and results are as follows:

[0073] 1. Proliferation detection:

[0074] NAML-6 cells and HAL-01 cells were counted and the cells were counted as 1×10 5 The cells were inoculated into 6-well plates at a density of 100 μg / mL, and drospirenone was added into the culture system according to a concentration gradient (0 μM, 20 μM and 40 μM). The cells were counted at 24 h, 48 h and 72 h of culture or the absorbance at a wavelength of 450 nM was measured after adding CCK-8. Growth curves were drawn. The results were shown in the figure. Figure 2 As shown in A.

[0075] Depend on Figure 2 As shown in Figure A, compared with the control group, both 20 μM drospirenone and 40 μM drospirenone can significantly inhibit the proliferation of ALL cell lines.

[0076] 2. Clone-forming ability test:

[0077] 1) Count NAML-6 cells and HAL-01 cells respectively and resuspend them to a cell density of 1×10 6 Cell suspension of 100 cells / mL;

[0078] 2) Add 500 μL of methylcellulose semisolid medium to a 1.5 mL EP tube, take 1 μL of cell suspension, i.e., 1000 cells, and add the medium. Then, add drospirenone at different final concentrations (0 μM, 20 μM, and 40 μM) and vigorously shake on a vortex mixer for 15 seconds.

[0079] 3) Let it stand for 20 minutes until the bubbles in the semi-solid medium dissipate, then slowly pipette and add it to the middle well of a 24-well plate. Gently shake the plate to evenly cover the wells.

[0080] 4) Add 1 mL of PBS to each well surrounding the sample well to seal the edges to prevent the semi-solid culture medium from drying out. Then transfer the wells to a 37°C incubator and culture for 10 days.

[0081] 5) On the 10th day of culture, the number of cell clones was recorded under a microscope. A colony with more than 50 cells was considered a clone. The cells were photographed using a 10× eyepiece and a 4× objective lens. The results were as follows: Figure 2 As shown in B.

[0082] Depend on Figure 2 B shows that compared with the control group, both 20 μM drospirenone and 40 μM drospirenone can significantly inhibit the clone formation of ALL cell lines.

[0083] 3. Cell cycle detection:

[0084] 1) Preparation of fixation buffer:

[0085] Solution 1 (2% formaldehyde): 20 μL formaldehyde plus 980 μL PBS;

[0086] Solution 2: 850 μL of anhydrous ethanol plus 400 μL of PBS;

[0087] Solution 3 (1% formaldehyde): 989 μL PBS plus 10 μL formaldehyde and 1 μL Tween-20;

[0088] Solution 4 (washing solution): 1 mL PBS plus 1 μL Tween-20;

[0089] Solution 5 (1% BSA): 1 mL PBS plus 1 μL Tween-20 and 0.01 g BSA;

[0090] FACS buffer (PBS containing 2% serum): 1 mL PBS plus 20 μL fetal bovine serum.

[0091] 2) NAML-6 cells and HAL-01 cells were treated with DMSO, 20 μM drospirenone, and 40 μM drospirenone, respectively. After 48 hours of treatment, 3 μL of bromodeoxyuridine (BrdU) solution (stock concentration: 10 mg / mL) was added to the culture system for every 1 mL of culture system. The cells were incubated at 37°C in the dark for 3 hours.

[0092] 3) Collect cells into a 1.5 mL EP tube, centrifuge at 500 g for 3 minutes, and discard the supernatant;

[0093] 4) Wash the cells twice with PBS and discard the supernatant;

[0094] 5) Add 1 mL of solution 1, fix at room temperature for 10 minutes, centrifuge at 5000 rpm for 5 minutes, and discard the supernatant;

[0095] 6) Add 1 mL of solution 2, fix on ice for half an hour, centrifuge at 5000 rpm for 5 minutes, and discard the supernatant;

[0096] 7) Add 1 mL of solution 3, fix on ice for at least 1 hour, centrifuge at 5000 rpm for 5 minutes, and discard the supernatant;

[0097] 8) Add 100 μL of 300 μg / mL DNase solution, gently pipette to mix, incubate at 37°C for 1 hour, centrifuge at 5000 rpm for 5 minutes, and discard the supernatant;

[0098] 9) Add 1 mL of solution 4 for washing, centrifuge at 5000 rpm for 5 minutes, and discard the supernatant;

[0099] 10) Add 100 μL of solution 5 to resuspend the pellet, add 2 μL of anti-BrdU, mix thoroughly by pipetting, incubate on ice in the dark for 30 minutes, centrifuge at 5000 rpm for 5 minutes, and discard the supernatant;

[0100] 11) Resuspend the pellet in 100 μL FACS buffer, add 1 μL 1 mg / mL DAPI solution (final concentration 10 μg / mL), add 0.5 μL RNase A, mix thoroughly by pipetting, and incubate at room temperature in the dark for 30 minutes.

[0101] 12) Flow cytometry was used to detect the levels of BrdU and DAPI in the cell samples; the results were as follows: Figure 3 shown.

[0102] Depend on Figure 3 It can be seen that compared with the control group, both 20μM drospirenone and 40μM drospirenone can significantly block the cell cycle of ALL cell lines, causing most cells to arrest in the G0-G1 phase and S phase.

[0103] Example 4 Inhibitory Effect of Methylprogesterone on ALL Cell Lines

[0104] The proliferation curve, colony formation ability and cell cycle of the ALL cell lines (NAML-6 cells and HAL-01 cells) after treatment with methyltestosterone were detected, and the detection method was the same as that described in Example 3. The results are shown in Figure 4 and Figure 5 .

[0105] As can be seen from Figure 4 A, compared with the control group, 20 μM methyltestosterone and 40 μM methyltestosterone can significantly inhibit the proliferation of the ALL cell lines.

[0106] As can be seen from Figure 4 B, compared with the control group, 20 μM methyltestosterone and 40 μM methyltestosterone can significantly inhibit the colony formation of the ALL cell lines.

[0107] As can be seen from Figure 5 , compared with the control group, 20 μM methyltestosterone and 40 μM methyltestosterone can significantly block the cell cycle of the ALL cell lines, and most of the cells are arrested in the G0-G1 phase.

[0108] Example 5 Inhibitory effect of conivaptan on ALL cell lines

[0109] The proliferation curve, colony formation ability and cell cycle of the ALL cell lines (NAML-6 cells and HAL-01 cells) after treatment with conivaptan were detected, and the detection method was the same as that described in Example 3. The results are shown in Figure 6 and Figure 7 .

[0110] As can be seen from Figure 6 A, compared with the control group, 20 μM conivaptan and 40 μM conivaptan can significantly inhibit the proliferation of the ALL cell lines.

[0111] As can be seen from Figure 6 B, compared with the control group, 20 μM conivaptan and 40 μM conivaptan can significantly inhibit the colony formation of the ALL cell lines.

[0112] As can be seen from Figure 7 , compared with the control group, 20 μM conivaptan and 40 μM conivaptan can significantly block the cell cycle of the ALL cell lines, and most of the cells are arrested in the G0-G1 phase.

[0113] The embodiments of the present application are described in detail above with reference to the drawings, but the present application is not limited to the above-described embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the spirit of the present application. Furthermore, the embodiments of the present application and the features in the embodiments can be combined with each other without conflict.

Claims

1. Use of an SRSF3 inhibitor in the preparation of a product for treating and / or preventing acute lymphoblastic leukemia, characterized in that: The SRSF3 inhibitor includes at least one of drospirenone, conivaptan and pharmaceutically acceptable salts thereof.

2. Use of a pharmaceutical composition in the preparation of a product for treating and / or preventing acute lymphoblastic leukemia, characterized in that: The pharmaceutical composition includes a SRSF3 inhibitor, and the SRSF3 inhibitor includes at least one of drospirenone, conivaptan, and pharmaceutically acceptable salts thereof.

3. The use according to claim 2, characterized in that The pharmaceutical composition further includes pharmaceutically acceptable excipients.

4. The use according to claim 3, characterized in that The pharmaceutically acceptable excipients include at least one of a binder, a disintegrant, a lubricant, a coating agent, a suspending agent, a thickening agent and a surfactant.

5. The use according to claim 2, characterized in that The administration of the product includes at least one of oral administration, enteral administration, subcutaneous injection, intramuscular injection, intravenous injection and intrathecal injection.

6. The use according to claim 2, characterized in that The dosage form of the product includes at least one of tablets, capsules, pills, injections, inhalants, suppositories, emulsion nanoparticles, powders, creams and jelly.

7. Use of an SRSF3 inhibitor in the preparation of an acute lymphoblastic leukemia cell line proliferation inhibitor, an acute lymphoblastic leukemia cell line apoptosis promoter, or an acute lymphoblastic leukemia cell line cell cycle arrester, characterized in that: The SRSF3 inhibitor includes at least one of drospirenone, conivaptan and pharmaceutically acceptable salts thereof.

8. The use according to claim 7, characterized in that The acute lymphoblastic leukemia cell line is a cell line that induces acute lymphoblastic leukemia.

9. The use according to claim 7, characterized in that The acute lymphoblastic leukemia cell lines include NAML-6 cells and / or HAL-01 cells.

10. Use of drospirenone and / or conivaptan in the preparation of an SRSF3 inhibitor for treating and / or preventing acute lymphoblastic leukemia.

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