Application of sodium polystyrenesulfonate in preparation of medicine for treating hepatocellular carcinoma
By using polystyrene sodium sulfonate (PSS) as an effective ingredient for hepatocellular carcinoma treatment, inhibiting the invasion and migration of liver cancer cells, solving the problem that the existing technology is difficult to prevent hepatocellular carcinoma metastasis and early development to middle and late stages, and achieving a significant inhibition of the development and metastasis of liver cancer.
Patent Information
- Application Number
- CN202510368262.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-26
- Publication Date
- 2025-05-13
AI Technical Summary
The prior art is difficult to effectively prevent the metastasis and early development of hepatocellular carcinoma to the middle and late stages, resulting in a poor prognosis.
Polystyrene sodium sulfonate (PSS) is used as an effective ingredient for hepatocellular carcinoma treatment, inhibiting the invasion and migration of liver cancer cells, reducing the relative content of potassium ions in the cell, leading to depolarization of the cell membrane, thereby inhibiting the development of liver cancer.
PSS can significantly inhibit the invasion and migration of liver cancer cells, reduce the risk of liver cancer metastasis, prevent hepatocellular carcinoma from early to middle and late stages, and has the advantages of high safety and few side effects.
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Figure CN119970784A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the field of drugs for treating hepatocellular carcinoma, and in particular to application of sodium polystyrene sulfonate in preparing drugs for treating hepatocellular carcinoma. Background Art
[0002] Primary liver cancer refers to a malignant tumor that occurs in liver cells or intrahepatic bile duct cells. According to statistics, about 85% of primary liver cancers are hepatocellular carcinoma (HCC). Due to the insidious onset of HCC, more than 70% of HCC patients are already in the middle or late stages when they are first diagnosed, and the prognosis is poor. Therefore, it is important to prevent the occurrence of HCC or prevent HCC from developing from the early stages to the middle or late stages. Therefore, it is of great significance to find drugs that can effectively prevent the metastasis of HCC to reduce the risk of HCC in high-risk groups.
[0003] Sodium polystyrene sulfonate (PSS) is a water-soluble polymer with strong dispersing and emulsifying properties. It can be used as a water treatment agent, emulsifier, cation exchange resin, etc. In the medical field, PSS has the effects of lowering blood lipids, blood pressure and blood sugar. In addition, it has certain applications in the preparation of anti-cancer drug delivery carriers, but its effect on cancer itself has not been reported. Summary of the invention
[0004] To solve the above problems, the present invention provides the use of sodium polystyrene sulfonate (PSS) in the preparation of a drug for treating hepatocellular carcinoma, wherein the PSS is used as an active ingredient for treating hepatocellular carcinoma rather than as a carrier of the active ingredient.
[0005] Furthermore, the application uses PSS as an effective ingredient for inhibiting the invasion or migration of liver cancer cells.
[0006] Furthermore, the application uses PSS as an effective ingredient for inhibiting liver cancer metastasis.
[0007] Preferably, the molecular weight of the PSS is 10,000-100,000, more preferably 50,000-80,000.
[0008] The invention also provides a medicine for treating hepatocellular carcinoma, wherein the effective component of the medicine comprises sodium polystyrene sulfonate.
[0009] Furthermore, the drug also includes a pharmaceutically acceptable carrier or excipient.
[0010] Furthermore, the drug is used to inhibit the invasion or migration of liver cancer cells.
[0011] Furthermore, the drug is used to inhibit liver cancer metastasis.
[0012] Furthermore, the drug is used to prevent hepatocellular carcinoma from developing from early stage to middle and late stage.
[0013] The inventors found in their research that PSS can effectively inhibit the invasion and migration of liver cancer cells in vitro, and reduce the relative content of potassium ions and depolarize the cell membrane in HCC cell lines, significantly inhibiting the development of liver cancer. At the same time, PSS has the advantages of high safety, few side effects, wide sources and easy synthesis. Therefore, PSS can effectively treat hepatocellular carcinoma, can effectively prevent the metastasis of hepatocellular carcinoma, and thus prevent hepatocellular carcinoma from developing from early stage to middle and late stage, and has great application prospects in the preparation of drugs for treating hepatocellular carcinoma.
[0014] The concept, specific structure and technical effects of the present invention will be further described below in conjunction with the accompanying drawings to fully understand the purpose, characteristics and effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Figure 1 The experimental results of the effect of PSS on cell migration in Example 1 are shown in the left side; the results of the cell migration experiment of HepG2 cells after adding PSS are shown in the right side; the results of the cell migration experiment of PLC cells after adding PSS are shown in the right side; the figure is drawn by GraphPadprism8.0 (*p<0.05, **p<0.001, ***p<0.0001, ****p<0.00001);
[0016] Figure 2 The experimental results of the effect of PSS on cell invasion in Example 2 are shown in the figure. The left side shows the results of the cell invasion experiment of HepG2 cells after adding PSS. The right side shows the results of the cell invasion experiment of PLC cells after adding PSS. The figure was drawn by GraphPadprism8.0 (*p<0.05, **p<0.001, ***p<0.0001, ****p<0.00001).
[0017] Figure 3 It is a statistical graph of the experimental results of the change of the relative potassium ion content in cells by PSS in Example 3; in the figure, A is the relative potassium ion content in cells detected by potassium ion fluorescent probe after HepG2 cells were added with PSS; B is the relative potassium ion content in cells detected by potassium ion fluorescent probe after PLC cells were added with PSS; the figure was drawn by GraphPadprism8.0 (*p<0.05, **p<0.001, ***p<0.0001, ****p<0.00001);
[0018] Figure 4It is a statistical graph of the experimental results of the effect of PSS on cell polarity in Example 4; Figure A shows the change in cell membrane polarity detected by DiBAC4(3) after the addition of PSS to HepG2 cells; Figure B shows the change in cell membrane polarity detected by DiBAC4(3) after the addition of PSS to PLC cells; the graph was drawn by GraphPadprism8.0 (*p<0.05, **p<0.001, ***p<0.0001, ****p<0.00001). DETAILED DESCRIPTION
[0019] The sodium polystyrene sulfonate (PSS) used in the present embodiment was purchased from Sigma, product number 243051, and the molecular weight was about 70,000.
[0020] Example 1 Effect of PSS on Cancer Cell Migration
[0021] Transwell Assay was used to detect the migration ability of human HCC cells (PLC and HepG2 cell lines). Cells were treated with or without PSS. 8 μm pore chambers (Greiner bio-one, 662638) and 24-well transwell plates (Greiner bio-one, 662160) were used.
[0022] When the cells are cultured to the logarithmic growth phase, digest the cells, wash the cells once with ice-cold 1× PBS, resuspend the cells in FBS-free high-glucose medium, count and plate. Add 5×10 4 cells (200 μL FBS-free high-glucose medium), 500 μL complete medium (10% FBS + 1% PS + high-glucose DMEM) was added to the lower chamber, the final concentration of PSS added to the PSS group was 10 nM, and the other group did not add PSS. Three replicates were set for each group. After 48 hours of incubation at 37°C, the cells that did not pass through the upper chamber were wiped off with a cotton swab, and the lower surface of the chamber was fixed with 4% paraformaldehyde at room temperature for 15 minutes, and 0.1% crystal violet was stained at room temperature for 15 minutes. The residual staining liquid on the cell surface was cleaned, and the cells were inverted to dry and examined under a microscope and photographed for statistics. The results are as follows Figure 1 As shown, the left side shows the results of cell migration experiment of HepG2 cells after adding PSS, and the right side shows the results of cell migration experiment of PLC cells after adding PSS; it can be seen from the figure that the number of cell migration in the group with 10nM PSS was significantly lower than that in the group without PSS; the above results show that after adding PSS, the migration ability of the two cancer cells is reduced.
[0023] Example 2 Effect of adding PSS on cell invasion
[0024] Transwell Assay was used to detect the invasion ability of human hepatocellular carcinoma HCC cells (HepG2 and PLC cell lines). PSS (10 nM) or no PSS was added to the cells. 8 μm pore chambers (Greiner bio-one, 662638) and 24-well transwell plates (Greiner bio-one, 662160) were used.
[0025] Thaw Matrigel (Corning, 356231) on ice, dilute Matrigel with ice-cold FBS-free high-glucose DMEM medium (gel: FBS free medium = 1:11), pipette 100 μL of diluted Matrigel into the upper chamber, and activate in a 37°C incubator for 2 hours. Digest the cells, wash the cells once with ice-cold 1× PBS, resuspend the cells with FBS-free high-glucose DMEM medium, count and plate. Add 5×10 4 cells (200 μL FBS-free high-glucose medium), 500 μL of 10% FBS + 1% PS + high-glucose DMEM medium was added to the lower chamber, the final concentration of PSS added to the PSS group was 10 nM, and the other group did not add PSS. Three replicates were set for each group. After culturing in a 37°C incubator for 48 hours, the cells that did not pass through the membrane in the upper chamber were wiped off with a cotton swab, and the lower surface of the chamber was fixed with 4% paraformaldehyde at room temperature for 15 minutes, and crystal violet was stained at room temperature for 15 minutes. The residual staining solution on the surface of the cells was washed, and the cells were inverted to dry and examined under a microscope and photographed for statistics. The results are as follows Figure 2 As shown, on the left are the results of cell invasion experiments of HepG2 cells after adding PSS; on the right are the results of cell invasion experiments of PLC cells after adding PSS; as can be seen from the figure, the number of cells invading in the group with 10nM PSS was significantly lower than that in the group without PSS; the above results indicate that after adding PSS, the invasion ability of the two cancer cells is reduced.
[0026] Example 3 Relationship between PSS and intracellular potassium ions in cancer cells
[0027] Human hepatocellular carcinoma cells (HCC): HepG2 and PLC cell lines were selected. PSS was added or not to treat the cells, and the relative potassium ion content in the cells was compared. The potassium ion fluorescent probe (IPG-4AM, ION Biosciences, 0321F) was used to detect the relative potassium ion content in the cells.
[0028] Specific detection steps: wait until the two HCC cells are in the logarithmic growth phase, digest the cells and resuspend them in 10% FBS + 1% PS high-glucose DMEM, count 10,000 cells per well (100 μL) and inoculate them into a 96-well plate, and add 100 μL of reagent to each well to divide them into three groups with final PSS concentrations of 10 nM, 5 nM and 0 nM. Set 3 replicates for each group of experimental conditions, incubate at 37°C for 1 hour, and detect the sample absorbance at 350 nm and 380 nm using an enzyme reader (model).
[0029] The results are as follows Figure 3 As shown in the figure, A is the relative content of potassium ions in HepG2 cells after adding PSS, and B is the relative content of potassium ions in PLC cells after adding PSS. It can be seen from the figure that the relative content of potassium ions in the cells of the two cancer cells is significantly reduced after adding PSS. The reduction of potassium ions can promote cell apoptosis, thereby inhibiting the growth of cancer cells.
[0030] Example 4 Relationship between PSS and cell membrane polarity of cancer cells
[0031] Human hepatocellular carcinoma cells (HCC): HepG2 and PLC cell lines were selected. PSS was added or not to treat the cells, and the changes in cell membrane polarity were compared. The potential-sensitive probe bis(1,3-dibarbituric acid)-trimethoxanol (DiBAC4(3), Thermo Fisher, B438) was used to detect changes in cell membrane polarity.
[0032] Specific detection steps: wait until the two HCC cells are in the logarithmic growth phase, digest the cells and resuspend them in 10% FBS + 1% PS high-glucose DMEM, count 10,000 cells per well (100 μL) and inoculate them into a 96-well plate, and add 100 μL of reagent to each well to divide them into three groups with final PSS concentrations of 10 nM, 5 nM and 0 nM. Set 3 replicates for each group of experimental conditions, incubate at 37°C for 1 hour, and detect the sample absorbance at 540 nm using an enzyme reader (model).
[0033] The results are as follows Figure 4 As shown in the figure, A shows the change of cell membrane polarity detected by DiBAC4(3) after adding PSS to HepG2 cells; B shows the change of cell membrane polarity detected by DiBAC4(3) after adding PSS to PLC cells. As can be seen from the figure, after adding PSS to the two cancer cells, the ion balance inside the cells is broken, the cells become hyperpolarized, the extracellular matrix is remodeled, EMT transformation is inhibited, and the growth of cancer cells can be inhibited.
[0034] The preferred specific embodiments of the present invention are described in detail above. It should be understood that a person skilled in the art can make many modifications and changes based on the concept of the present invention without creative work. Therefore, any technical solution that can be obtained by a person skilled in the art through logical analysis, reasoning or limited experiments based on the concept of the present invention on the basis of the prior art should be within the scope of protection determined by the claims.
Claims
1. Use of sodium polystyrene sulfonate in the preparation of a drug for treating hepatocellular carcinoma, characterized in that: The application uses PSS as an effective ingredient for treating hepatocellular carcinoma.
2. The use of sodium polystyrene sulfonate according to claim 1 in the preparation of a drug for treating hepatocellular carcinoma, characterized in that: The application uses PSS as an effective component for inhibiting the invasion or migration of liver cancer cells.
3. Use of sodium polystyrene sulfonate according to claim 1 in preparing a drug for treating hepatocellular carcinoma, characterized in that: The application uses PSS as an effective component for inhibiting liver cancer metastasis.
4. A drug for treating hepatocellular carcinoma, characterized in that: The active ingredient includes sodium polystyrene sulfonate.
5. The drug for treating hepatocellular carcinoma according to claim 4, characterized in that Also included are pharmaceutically acceptable carriers or excipients.
6. The drug for treating hepatocellular carcinoma according to claim 4, characterized in that The drug is used to inhibit the invasion or migration of liver cancer cells.
7. The drug for treating hepatocellular carcinoma according to claim 4, characterized in that The drug is used for inhibiting liver cancer metastasis.
8. The drug for treating hepatocellular carcinoma according to claim 4, characterized in that The medicine is used for preventing hepatocellular carcinoma from developing from early stage to middle and late stage.