CN111728990A - Application of Babaodan in preparing medicine for preventing and treating liver cancer - Google Patents
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- CN111728990A CN111728990A CN201911021056.4A CN201911021056A CN111728990A CN 111728990 A CN111728990 A CN 111728990A CN 201911021056 A CN201911021056 A CN 201911021056A CN 111728990 A CN111728990 A CN 111728990A
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Abstract
The invention relates to the field of traditional Chinese medicines, in particular to application of Babaodan in preparing a medicine for preventing and treating liver cancer. The invention discloses the prevention and treatment effects of Babaodan on liver cancer solid tumors and late ascites tumors. The mechanism of action is to generate anti-tumor cell proliferation by inhibiting JAK/STAT signal pathway activation. It is further clear that this effect is an inhibition of the pro-tumor inflammatory pathway by inhibiting phosphorylation of STAT 3. And moreover, the compound can activate lymphocytes in ascites to secrete and express IFN-gamma, remarkably prolongs the survival time of tumor-bearing mice, and has great application prospect of tumor medicaments.
Description
Technical Field
The invention relates to the field of traditional Chinese medicines, in particular to application of Babaodan in preparing a medicine for preventing and treating liver cancer.
Background
The eight-treasure pill is a national Chinese medicine secret variety and has the efficacies of clearing away heat and dampness, promoting blood circulation, removing toxicity, removing jaundice and relieving pain. It is suitable for patients with fever, jaundice, dark urine, nausea, emesis, anorexia, hypochondriac pain, abdominal distention, yellow greasy or thick greasy tongue fur, or urethra burning pain and pain due to downward flow of damp-heat, infectious viral hepatitis, acute cholecystitis, acute urinary infection, etc. Accordingly, the prior art discloses the therapeutic effects of the eight-treasure pill on liver and gallbladder and urinary system, such as liver failure treatment and jaundice reduction (CN201811462399, CN 201711084134). The prior art suggests that its therapeutic action may be related to its anti-inflammatory action. Tumors are a type of chronic disease with high heterogeneity, and chronic inflammation in the long term is one of its typical features. Therefore, the research aims to observe the action and the related mechanism of the Babaodan in the prevention and treatment of the cancer through in vivo and in vitro experiments.
Hepatocellular carcinoma (HCC) is one of the most common liver tumors. The closest prior art discloses: (1) babaodan can be used for preventing recurrence after early stage hepatocarcinoma (CN 201611065626); (2) the Babaodan can reduce the inflammatory infiltration of primary liver cancer and fatty liver tissue microenvironment species by inhibiting a TLP4 signal path, thereby playing a role in inhibiting the development of liver cancer (Zhaonanli, the influence of Babaodan on primary liver cancer and fatty liver and the mechanism research thereof [ D ], Shanghai, second military, 2017). Compared with the closest prior art, the invention discloses the application of Babaodan in the late ascites transfer of liver cancer. The prior literature also discloses a close relationship between the inflammation-related pathway JAK/STAT and the occurrence and development of liver cancer, and suggests that STAT6 downstream of the pathway has high clinical diagnosis and prognosis evaluation values (int.J. Oncol, 2019,55(4) 805-822). The invention discloses inhibition of baobandan on activation of JAK/STAT pathway downstream STAT3, thereby causing significant reduction in inflammatory factor levels.
Therefore, the invention expands the new indications of the Babaodan and shows better prevention and/or treatment value for JAK/STAT activated subtype liver cancer patients or late ascites transfer patients. Specifically, babaodan acts by inhibiting STAT3 phosphorylation activation.
Disclosure of Invention
The invention aims to provide application of Babaodan in preparing a medicament for preventing and treating liver cancer.
In order to realize the purpose, the invention adopts the following technical scheme:
in particular, the method comprises the following steps of,
the eight-treasure pill comprises calculus bovis, fel Serpentis, cornu Saigae Tataricae, Margarita powder, Notoginseng radix, and Moschus as main ingredients; preferably Babaodan of Xiamen Chinese medicine factory Co.
In particular, the method comprises the following steps of,
the application comprises the application of the Babaodan in preparing the medicine for preventing liver cancer.
The application comprises the application of the Babaodan in preparing the medicine for treating liver cancer.
The application comprises that the Babaodan inhibits STAT3 phosphorylation to play a role in resisting liver cancer.
In vitro on the liver cancer cells, MTT method is adopted to detect the proliferation inhibition effect of the babaodan with different concentrations on the liver cancer cells, and the influence of the babaodan on the STAT3 phosphorylation of the liver cancer cells is observed through Western blot. The mouse liver cancer solid cancer model is copied, the eight-treasure pill is orally taken, and the influence of the eight-treasure pill on the liver cancer solid cancer sub-volume is observed. The eight-treasure pill is orally administrated, a mouse liver cancer ascites cancer model is copied and continuously administrated, the influence of the eight-treasure pill on the weight of the liver cancer is observed, and the influence on the ascites is judged. The eight-treasure pill is orally taken to duplicate a mouse liver cancer solid tumor model, and the influence of preventive administration of the eight-treasure pill on the liver cancer tumor rate and the tumor time is observed. On the liver cancer ascites cancer model, the effect of the babaodan on the phosphorylation of the STAT3 of the liver cancer cell, the expression of the relevant genes of inflammation and the immune activation is observed. The eight-treasure pill is orally taken to copy a mouse liver cancer solid tumor model, and the tumor size, the tumor formation time and the tumor formation rate are observed.
Specifically included are the following items which,
(1) the eight-treasure pill has proliferation inhibiting effect on hepatocarcinoma cell
(2) The therapeutic effect of BABAO pill on liver cancer solid tumor is achieved by inhibiting
(3) Natural eight-treasure pill for treating liver ascites carcinoma
(4) Inhibition effect of Babaodan on phosphorylation of inflammation pathway key protein STAT3 on in-vitro human liver cancer cells
(5) The Babaodan can inhibit the activation level of inflammation key pathway molecule STAT3 on an H22 ascites cancer model
(6) The BABAODAN can inhibit the level of inflammatory factors on an H22 ascites cancer model
(7) Enhancement of IFN gamma secreting lymphocytes number and intensity by Babaodan in H22 ascites carcinoma model
(8) The eight-treasure pill has prevention effect on the mouse liver cancer solid tumor
The result shows that the eight-treasure pill has proliferation inhibiting effect on liver cancer cells in vitro and shows certain dose dependence, and the eight-treasure pill has certain inhibition effect on human liver cancer cell STAT3 phosphorylation in vitro. The eight-treasure pill has certain treatment effect on the liver cancer solid tumor and ascites cancer, has prevention effect on the liver cancer solid tumor, and can inhibit STAT3 phosphorylation, inhibit inflammation level in a tumor microenvironment and obviously enhance immune activation in vivo, particularly natural eight-treasure pill.
Detailed Description
The term "JAK/STAT signaling pathway" is a common pathway for numerous cytokine signaling, is widely involved in processes such as cell proliferation, differentiation, apoptosis, and inflammation, and can be regulated by various pathways such as interaction of negative regulators with other signaling pathways, covalent modification of STATs, and the like. STAT protein families include STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT 6.
The term "STAT 3" belongs to one of the STAT family members and is a regulatory element downstream of the JAK/STAT signaling pathway that, when activated by phosphorylation, forms a dimeric transcription factor into the nucleus activating transcription of downstream target genes.
The medicine of the present invention may be prepared through conventional process, such as preparing bolus, powder, ointment, pellet, etc. Preferably, the Chinese medicinal preparation is selected as a pellet.
Drawings
FIG. 1 the effect of Babaodan on the proliferation of hepatoma cells. Adding artificial Babaodan (black column or round dot curve) or natural Babaodan (gray column or square curve) with different concentrations into a cell culture system, observing the influence on the cell activity of a mouse liver cancer cell line Hepa1-6(A) and a human liver cancer cell line LM3(B), and detecting the cell activity by an MTT method 72 hours after the Babaodan is treated. P <0.05, p <0.001, p < 0.0001.
FIG. 2 the effect of Babaodan on the growth of solid tumor of liver cancer. The artificial eight-treasure pill has the effect of inhibiting the volume of Hepa1-6 liver cancer solid tumor (A) and H22 liver cancer solid tumor (B). P <0.05, p <0.01, p <0.001, p < 0.0001.
FIG. 3 shows the effect of natural Babaodan on ascites carcinoma of liver cancer. The weight change of mice on the fifth day (A) and the sixth day (B) of the mice of the liver cancer ascites model treated by the eight-treasure pill, and the ascites generation amount of mice of the treatment group and the control group of the eight-treasure pill on the eighth day of the mice of the liver cancer ascites model treated by the eight-treasure pill (C). P < 0.05. (C) Cell clones were obtained by hanging drop culture of 4T1-wt or 4T1-ApoA1 cells and then plated on collagen type I coated 96-well cell culture plates. Monitoring is performed at the corresponding time points.
FIG. 4 shows the effect of Babaodan on the phosphorylation of STAT3, a key protein in the pathway of human hepatoma cell inflammation. Western blot detects STAT3 phosphorylation level, and GAPDH is used as an internal control.
Figure 5 effect of natural babaodan on activation level of STAT3 key pathway molecule of inflammation in H22 ascites cancer model. The results showed that the ascites cells from the natural eight-treasure treatment group had significantly reduced levels of STAT3 phosphorylation, # p < 0.01.
FIG. 6 Effect of Babaodan on the level of inflammatory factors in the H22 ascites carcinoma model.
FIG. 7 Effect of Babaodan on the number and intensity of IFN γ -secreting lymphocytes in the H22 ascites carcinoma model. H22 ascites cancer model, treating as before, killing tumor-bearing mice 10 days after the natural Babaodan stomach-filling therapy with the medium dosage, respectively taking tumor tissues and spleen tissues, and homogenizing to respectively prepare tumor tissue cell suspensions and spleen tissue cell suspensions. Tumor tissue cell suspension is tested for activity of specific anti-tumor immune cells by ELISpot, black spots in the figure represent the number and intensity of IFN gamma-secreting lymphocytes, and the more and the larger the number of spots, the higher the number and activity of surface immune activated cells. The number and intensity of IFN gamma-secreting lymphocytes from the spleen tissue cell suspension were measured after co-culturing the spleen tissue cell suspension with H22 cells.
FIG. 8 the effect of Babaodan on the prevention of liver cancer solid tumors in mice. (A) The effect of the prophylactic administration of Babaodan on the volume of Hepa1-6 liver cancer solid tumors. (B) The effect of the preventive administration of Babaodan on the tumor formation time of Hepa1-6 liver cancer solid tumor.
Detailed Description
The invention will be further explained and illustrated with reference to specific examples, which are, however, to be understood as being given by way of illustration only and not in any way limitative of the invention.
The experimental device materials and reagents related to the invention are as follows:
(1) laboratory animal
Male SPF grade C57BL/6 and Balb/C mice at 6-8 weeks of age were purchased from the university of Nanjing model animal institute. Animal license number: SCXK (Su) 2015-0001, the experimental animals were raised in an IVC independent isolated air supply system, and the animals were fed with free food and water.
(2) Medicaments and agents
Babaodan (Xiamen Chinese medicine factory Co., Ltd., product batch No. 160603); the BCA protein concentration detection kit (P0010), the MTT reagent (C0009), the primary anti-diluent (P0023A) and the cell lysate (P0013) are purchased from Shanghai Bin Yuntian Biotech limited; protease inhibitors (11873580001, Roche); WB ECL luminescent liquid (WBKLS0500, Millipore); total RNA extraction reagent Trizol (15596-026, Invitrogen); HRP-labeled secondary antibodies (GAR007and GAM007, Multisciences,1:2000 dilution); anti-GAPDH (MB001, Bioworld, 1:2000 dilution), anti-pSTAT 3(9145S, Cell Signaling Technology); reverse transcription reagent PrimeScript RT Master MixPerfect Real Time (DRR0036A, TaKaRa); faststart Universal SYBR Green Master (04913914001, Roche); ELISpot: cell strainer (352350, BD FALCON); human lymphocyte separation medium (Tianjin tertiary biological products science and technology limited); trypan blue (C0011, cloudy day); mouse IFN-. gamma.ELISpot (3321-2A, MABTECH); syringes (Shandongwei high-polymer products Co., Ltd.); collagenic IV (17104-; human recombinant IL-6(10395-HNAE), murine recombinant IL-6(50136-MNAE) were purchased from Beijing Yiqiao Shenzhou Biotech, Inc.
The primers were synthesized by Nanjing Kingsrei Biotechnology Inc., and the sequences of the primers were as follows:
(3) method of producing a composite material
3.1 model preparation
Ascites carcinoma model of liver cancer
Selecting 8-10 week-old male C57BL/6 mice, administering artificial and natural Babaodan intragastric therapy twice a day, wherein the dose of each time is 250mg/kg, injecting 5 multiplied by 10^6 cells into the abdominal cavity of each mouse 28 days after intragastric administration, starting to detect the weight change of the mice on the third day, and extracting ascites to detect after the ascites grows out.
Solid cancer model of liver cancer
Hepa1-6 subcutaneous tumor model: male C57BL/6 mice of 6-8 weeks of age were selected and treated according to the experimental design by subcutaneous injection of 2X 10^6 Hepa1-6 cells per mouse.
H22 subcutaneous tumor model: selecting male Balb/c mice with the age of 6-8 weeks, injecting 5 multiplied by 10^5 cells into each mouse subcutaneously, and starting treatment when the tumor diameter is about 5 mm.
Prevention model of liver cancer solid cancer
Selecting 6-8 weeks old male C57BL/6 mice, according to the experimental design, the mice are continuously administered with natural Babaodan for intragastric therapy for seven days one week before the tumor formation, after seven days, each mouse is injected with 2 x 10^6 Hepa1-6 cells subcutaneously, and the tumor formation condition of each group of mice is observed.
3.2 grouping and administration
Mice were divided into a control group (control), an artificial babysbreath group (250mg/kg), and a natural babysbreath group (250mg/kg) by a weight stratification randomization method, each group containing 10 mice. After the mice are adaptively raised for one week, the mice are administered twice a day by intragastric administration according to body weight, and the dose of each time is 250 mg/kg.
3.3 sample Collection and processing
Ascites tumor: after the mouse grows the ascites, a 5ml disposable syringe is used for injecting at the lower edge position of the mouse abdominal cavity to extract the ascites, the ascites is centrifuged for 5 minutes at 2000r/min, cell sediment is collected, total protein and RNA are extracted from the cells, and the phosphorylation STAT3 level and the related inflammatory factor expression level are detected by western blot and qPCR respectively.
Solid tumors: immediately separating out a tumor and a spleen after a mouse dies, and digesting the tumor with collagenase to prepare a single cell suspension; after spleen grinding, lymphocyte separation liquid is added, lymphocytes are separated by centrifugation, and immune activation is detected by ELISpot.
3.4 Observation items and methods
Typical conditions include mouse body weight, tumor size and survival time, etc.
Detecting the activation condition of phosphorylated STAT3 in the ascites tumor of the mouse through Western blot and phosphorylated STAT3 in the ascites of the mouse after the treatment of babaodan, extracting the total cell protein in the ascites, calculating the amount of the calculated sample after the protein concentration is measured through a BCA method, and detecting the activation condition of phosphorylated STAT3 through Western blot; the effect of babaodan on the activation of phosphorylated STAT3 at the cellular level was examined: culturing Hepa1-6 and LM3 cells, laying 6 pore plates, laying 3 x 10^5 cells per pore, adding 1mg/ml Babaodan water extract after overnight culture, treating for 12h, adding mouse and human IL-6(25ng/ul) respectively after 12h, stimulating for 30min, collecting cells after 30min, extracting total cell protein, calculating sample loading amount after measuring protein concentration by BCA method, and detecting phosphorylation STAT3 expression by western blot.
The qPCR method is used for detecting the expression levels of IL-1beta, IL-6, TNF-alpha, STAT3 and COX2 related inflammatory factors in the ascites: extracting total RNA in ascites cells, carrying out Reverse transcription reaction according to the instruction of a Takara Reverse transcription kit, wherein the reaction system is Reverse transcription Mix 2ul, the RNA is 500ng, DEPC water is added to supplement 10ul, and the reaction conditions are 37 ℃ for 30min and 85 ℃ for 5 s; taking cDNA as a template, preparing 10ul of a reaction system by using SYBR Green fluorescent dye for amplification, wherein the reaction system is SYBR Green Mix 10ul, a primer F0.6 ul, a primer R0.6 ul and cDNA 2ul, adding DEPC water to supplement 20ul, and the reaction conditions are 95 ℃ for 5min, 95 ℃ for 10s, 60 ℃ for 30s, 40 cycles, 95 ℃ for 15s, 60 ℃ for 60s, 95 ℃ for 15s and 25 cycles. Relative expression of the gene was calculated using 2- Δ Ct with GAPDH as an internal control.
Culturing Hepa1-6 and LM3 cells in MTT, laying 96-well plates, laying 8000 cells in each well, culturing overnight, adding 100ul diluted medicine, treating for 72h, discarding culture solution in the plate after 72h, adding 100ul 0.5mg/ml MTT working solution in each well, culturing for 3h, discarding the MTT working solution, adding 150ul isopropanol in each well, shaking the 96-well plates on a shaking bed for 15min, measuring absorbance value at 570nm after 15min, and determining relative cell activity (%) as (experimental group-blank control group)/(control group-blank control group) × 100% according to the formula
3.5 cell culture and treatment
The cell culture Hela1-6 and LM3 were cultured in DMEM medium containing 10% FBS and 1% penicillin-streptomycin, and H22 was cultured in RPMI 1640 medium containing 10% FBS and 1% penicillin-streptomycin, wherein the FBS, penicillin-streptomycin, DMEM and RPMI 1640 media were purchased from Gibco, and the cells were cultured in a cell culture chamber at 37 ℃ and 5% CO 2.
Babaodan aqueous extract treatment cells to prepare 10mg/ml Babaodan aqueous extract as an example, a 15ml centrifuge tube is taken, 100mg of Babaodan is weighed by an analytical balance, 9ml of RPMI 1640 culture medium (without serum and antibiotics) is added into an ultra-clean bench, after shaking, ultrasonic treatment is carried out for 30min in an ice bath, a 0.22um filter is used for filtration, 1ml of FBS is added into the filtrate, and the 10mg/ml aqueous extract is obtained after uniform mixing.
3.6 statistical methods
The data were statistically and analytically plotted using Graphpad Prism 7.0 software. The data were expressed as mean ± standard deviation (mean ± SD), and two-by-two comparisons using a one-way analysis of variance between groups were expressed as Sidak' smart complexes, p <0.05, p <0.01, p <0.001, p < 0.0001.
Example 1: the eight-treasure pill has proliferation inhibiting effect on hepatocarcinoma cell
The results in fig. 1 show that the activity of babaodan in inhibiting the proliferation of hepatoma cells is dose-dependent. Moreover, in most cases, the natural Babao pill has better inhibition effect on liver cancer cell proliferation than the artificial Babao pill, especially the natural Babao pill has more than 90% inhibition effect on hepatoma 1-6 cells under the concentration of 2.5mg/ml, and the artificial Babao pill with the same dosage has only 10-20% inhibition effect. Therefore, the eight-treasure pill has proliferation inhibiting effect on liver cancer cells and shows certain dose dependence; the natural Babao pill has better effect than the artificial Babao pill.
Example 2: therapeutic effect of Babaodan on liver cancer solid tumor
We observed the therapeutic effect of Babaodan through a mouse liver cancer solid tumor model. The results in FIG. 2A show that the low dose (250mg/kg) and high dose (500mg/kg) of the artificial babysbreath significantly inhibited the growth of tumors in the liver cancer model of Hepa1-6 compared to the control group. The results in fig. 2B show that the tumor volume of mice with low artificial eight-treasure pill dose (250mg/kg) was significantly smaller than that of the control group (P <0.01) in the H22 liver cancer solid tumor model, and the tumor growth was significantly inhibited. Therefore, the artificial eight-treasure pill has obvious treatment effect on the liver cancer solid tumor.
Example 3: functional evaluation of AD5-ApoA1 virus
The results of the body weights of the mice in FIGS. 3A-B show that the increase in body weight of the mice in the natural Babaodan-treated group was significantly delayed compared to the control group, indicating that ascites formation was slow. There were significant differences between 5 and 6 days after tumor inoculation. Ascites was extracted on day 8, and the change in body weight of each mouse (reflecting the total amount of ascites generated in each mouse) before and after the extraction of ascites was examined, the results showed that the ascites amount in the natural babaodan-treated group was significantly lower than that in the control group (fig. 3C). Therefore, the natural Babaodan has obvious treatment effect on the liver cancer ascites carcinoma.
Example 4: inhibition effect of Babaodan on phosphorylation of inflammation pathway key protein STAT3 on in-vitro human liver cancer cells
The results in FIG. 4 show that the phosphorylation of STAT3 was slightly increased after 30 minutes of IL-6 stimulation of human LM3 hepatoma cells, and that the phosphorylation of STAT3 caused by IL-6 stimulation could be reduced by pre-treating human LM3 hepatoma cells for 12 hours with artificial or natural Babaodan. Therefore, the eight-treasure pill has certain function of inhibiting inflammatory pathways in vitro.
Example 5: the Babaodan can inhibit the activation level of inflammation key pathway molecule STAT3 on an H22 ascites cancer model
In the H22 ascites cancer model, the treatment was performed as before, on the eighth day, the ascites was extracted, the ascites cell protein was extracted, and the extracted protein was quantified and then the sample was examined by Western blot, and the results showed that STAT3 activation was significantly inhibited in the natural Babaodan treatment group (FIG. 5A). Comparing the gray value of pSTAT3 of each histone electrophoresis with the GAPDH internal reference, the relative expression amount is obtained (fig. 5B), and the result shows that the natural babaodan can remarkably reduce the phosphorylation level of the inflammation pathway key molecule STAT 3. Therefore, the eight-treasure pill has the function of inhibiting inflammatory pathways in a body.
Example 6: the BABAODAN can inhibit the level of inflammatory factors on an H22 ascites cancer model
On an H22 ascites cancer model, ascites is extracted on the eighth day, total RNA of ascites cells is extracted, and the expression of inflammation related genes such as interleukin 1(IL-1beta), interleukin 6 (IL-6), tumor necrosis factor (TNFa), signal transduction transcription activator 3(STAT3) and cyclooxygenase 2(COX2) is quantitatively detected by qRT-PCR. The results (FIG. 6) show that although there is no statistical difference compared with the control group, the expression level of the inflammatory factors in the ascites cells of the mice of the natural Babaodan treated group has a certain degree of down-regulation trend. Therefore, the eight-treasure pill has certain in-vivo inflammation pathway inhibiting effect.
Example 7: enhancement of IFN gamma secreting lymphocytes number and intensity by Babaodan in H22 ascites carcinoma model
The results are shown in fig. 7, in which the number of cells secreting Gamma interferon (IFN γ) was significantly increased in the tumor tissue-derived cells of the medium-dose octadan-treated group compared to the control group. Similarly, when spleen cells derived from the medium-dose octave-treated group were co-cultured with H22 cells, the number of cells secreting Gamma interferon (IFN γ) was also found to be significantly increased in spleen cells derived from the medium-dose octave-treated group, as compared to the control group (fig.). Therefore, the eight-treasure pill has certain in-vivo immune activation effect.
Example 8: the eight-treasure pill has prevention effect on the mouse liver cancer solid tumor
The results in fig. 8A show that both the artificial and natural eight-treasure Dan prevention groups showed a definite reduction in mean tumor volume compared to the control group, although there was no statistically significant difference (P > 0.05). For the tumor formation rate, the medium dose group of the natural Babao pill is mainly observed, and the results in table 1 show that the tumor formation rate of the natural Babao pill group is 62.5% and the tumor inhibition rate is 37.5% on the 5 th day after tumor inoculation; the tumor formation rate on the 7 th day is 87.5 percent, and the tumor inhibition rate is 12.5 percent; on the 7 th day, the control group had developed tumors. The results of the tumor formation rate show that the natural Babaodan can obviously delay the formation of tumors. The results in fig. 8B show that the mean time to tumor was 3.6 days for the control group (black bars), which was significantly longer and significantly different (p <0.05) than the mean time to tumor of 4.9 days for the eight-treasure treatment group. The results show that the natural Babaodan has definite prevention effect on liver cancer. The results show that the natural Babaodan has definite prevention effect on the mouse liver cancer solid tumor.
From the above results, the invention provides the use of the eight-treasure pill for preventing and/or treating liver cancer. The Babaodan can inhibit the proliferation of liver cancer cells, has certain prevention and treatment effects on liver cancer, and can be realized by inhibiting STAT3 phosphorylation, inhibiting inflammation level in a tumor microenvironment and obviously enhancing immune activation.
Claims (7)
1. An application of Babaodan in preparing a medicine for preventing and treating liver cancer is characterized in that: the application is the application of the Babaodan in preparing the JAK/STAT signal pathway resisting medicine.
2. Use according to claim 1, characterized in that: the application of the JAK/STAT resistant signal channel medicine comprises a factor for regulating and controlling downstream mediated inflammation of a channel.
3. Use according to claim 2, characterized in that: the factors comprise STAT protein families including STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT 6.
4. Use according to claim 2, characterized in that: the regulation relates to the regulation of protein modification pathways such as phosphorylation, methylation, acetylation, glycosylation, ubiquitination and the like of STAT protein families.
5. Use according to claims 1 to 4, characterized in that: the effect of the Babaodan for preventing and treating liver cancer is to mediate the activation of inflammatory factors by inhibiting the phosphorylation of STAT 3.
6. Use according to claim 1, characterized in that: the liver cancer comprises primary liver cancer and secondary liver cancer.
7. Use according to claim 6, characterized in that: the secondary liver cancer comprises ascites metastatic liver cancer and solid metastatic liver cancer.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569637A (en) * | 2022-03-16 | 2022-06-03 | 厦门中药厂有限公司 | Application of Babaodan in preparation of NF-kB-UPS signal channel inhibitor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108114010A (en) * | 2016-11-28 | 2018-06-05 | 厦门中药厂有限公司 | Purposes of the pill of Eight Treasures in the drug for preparing prevention early liver cancer postoperative recurrence |
| CN109303791A (en) * | 2017-07-28 | 2019-02-05 | 中国科学院上海生命科学研究院 | The new function and purposes of pill of Eight Treasures |
-
2019
- 2019-12-23 CN CN201911021056.4A patent/CN111728990A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108114010A (en) * | 2016-11-28 | 2018-06-05 | 厦门中药厂有限公司 | Purposes of the pill of Eight Treasures in the drug for preparing prevention early liver cancer postoperative recurrence |
| CN109303791A (en) * | 2017-07-28 | 2019-02-05 | 中国科学院上海生命科学研究院 | The new function and purposes of pill of Eight Treasures |
Non-Patent Citations (8)
| Title |
|---|
| 兰水中等: "《常见病方剂新用法》", 31 May 2017, 北京名医世纪文化传媒有限公司 * |
| 冯正权等: "八宝丹配合介入治疗热毒血瘀型原发性肝癌的临床观察", 《中华中医药学刊》 * |
| 无: "八宝丹", 《康爱多》 * |
| 李梅: "八宝丹的功效与作用是什么", 《有来医生》 * |
| 李洪伦等: "八宝丹在恶性肿瘤治疗中的应用探索", 《滨州医学院学报》 * |
| 柯樱等: "八宝丹的临床应用研究进展", 《中成药》 * |
| 赵娜萍: "八宝丹对原发性肝癌和脂肪肝的影响及机制研究", 《中国博士学位论文全文数据库》 * |
| 陈曦等: "八宝丹治疗肝病临床研究进展", 《中华中医药学刊》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569637A (en) * | 2022-03-16 | 2022-06-03 | 厦门中药厂有限公司 | Application of Babaodan in preparation of NF-kB-UPS signal channel inhibitor |
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