CN112137999A - Application of dronedarone hydrochloride in preparation of medicine for resisting digestive tract tumor - Google Patents
Application of dronedarone hydrochloride in preparation of medicine for resisting digestive tract tumor Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The application discloses an application of dronedarone hydrochloride in preparing a medicine for resisting digestive tract tumors, wherein the dronedarone hydrochloride has a chemical name: the method comprises the following steps of firstly, specifically evaluating the effect of dronedarone hydrochloride in an esophageal cancer in-vitro experiment through the effect of dronedarone hydrochloride on an esophageal cancer cell line; and secondly, specifically evaluating the in-vitro inhibition effect of the dronedarone hydrochloride on the gastric cancer cell line through the effect of the dronedarone hydrochloride on the gastric cancer cell line, and comprehensively evaluating the effect of the dronedarone hydrochloride on the digestive tract tumor. The result shows that the dronedarone hydrochloride with proper concentration has better inhibition effect in a digestive tract tumor cell line, and provides a new idea and a new basis for treating and preventing tumors.
Description
Technical Field
The application belongs to the field of biological medicines, and particularly relates to application of dronedarone hydrochloride in preparation of a medicine for resisting digestive tract tumors.
Background
Esophageal Cancer (EC) is one of eight common malignant tumors worldwide, and data investigated by the world health organization and the international cancer research institute (WHO/IARC) show that about 45.6 ten thousand new cases of esophageal cancer account for 3.2% of all cancers worldwide in 2012; the number of deaths is about 40 million, accounting for 4.9% of all cancer deaths. China is a high-incidence country of esophageal cancer and the country with the highest incidence of esophageal cancer, and the incidence rate of the Chinese is 5 th of various tumors in the continental region of China and the incidence rate of the Chinese is 4 th. The incidence of esophageal cancer is obviously different in China, and the absolute high incidence of certain areas is clearly contrasted with the relative low incidence of peripheral areas, so that the most typical epidemiological characteristics of esophageal cancer in China are formed. According to epidemiological survey in 2018, the survival rate of 5 years after esophageal cancer operation is 5-20%. Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) are the two major histological types of esophageal cancer. ESCC is the most common subtype in developing countries, and one of the main causes of low 5-year survival of esophageal squamous cells is due to high recurrence rate after first surgery. At present, radiation therapy and chemotherapy are mainly used for preventing postoperative recurrence of esophageal cancer, but serious side effects brought to a body after radiation therapy and chemotherapy enable radiotherapy and chemotherapy to extend the life of a patient and also aggravate adverse conditions of prognosis of the patient. And the 5-year survival rate of esophageal cancer patients is still not significantly improved. Gastric cancer is one of the common digestive tract malignancies and the fourth most common cancer in the world. Over 70% of the disorders occur in developing countries, and patients have a 5-year survival rate of less than 20%, resulting in 100 million deaths worldwide each year. Although surgical resection and effective assistance are performed at an early stage of a disease, the gastric cancer is still a large cancer threatening the life and health of a patient due to poor prognosis and low early diagnosis rate of the patient, and serious side effects of radiotherapy and chemotherapy on the body. Therefore, the discovery of a novel therapeutic agent for gastric cancer is of great significance.
N- [ 2-butyl-3- [4- [3- (dibutylamino) propoxy ] phenyl ] -5-benzofuranyl ] -methanesulfonamide (Dronedarone hydrochloride, molecular formula: C31H45ClN2O5S, molecular weight: 593.217, CAS: 141625-93-6) is a novel antiarrhythmic drug approved by the FDA in the United states. It is reported in the literature to be a multichannel blocker with various electrophysiological properties for maintaining the sinus rhythm in patients with non-permanent atrial fibrillation.
Disclosure of Invention
The invention aims to provide application of dronedarone hydrochloride in preparation of anti-digestive tract tumor drugs, and the relationship between dronedarone hydrochloride and tumors is preliminarily researched through in vitro experiments, so that dronedarone hydrochloride is proved to have an inhibiting effect on tumor cells. Wherein the tumor includes but is not limited to esophageal cancer, gastric cancer and the like.
Based on the above purpose, the technical scheme adopted by the invention is as follows:
application of dronedarone hydrochloride in preparation of medicine for inhibiting tumor cell proliferation
Specifically, when the dronedarone hydrochloride is used for the esophageal cancer cell lines KYSE150 and KYSE450, the dronedarone hydrochloride can inhibit the proliferation of esophageal squamous cell carcinoma cells and the quantity and the size of clone formation when the concentration of the dronedarone hydrochloride is 1-2.5 mu M. When the dronedarone hydrochloride is used for gastric cancer cell lines HGC27 and AGS, the dronedarone hydrochloride can inhibit proliferation of gastric cancer cells and the quantity and size of clone formation when the concentration is 1-2.5 mu M.
Application of dronedarone hydrochloride in preparation of medicine for inhibiting mouse tumor growth in human-derived esophageal squamous carcinoma transplanted tumor model
Specifically, when the dronedarone hydrochloride is used for the esophageal cancer human tumor xenograft model, the toxic and side effects on animals are small when the dronedarone hydrochloride is below 120 mg/kg/day, and the tumor growth can be obviously inhibited when the dronedarone hydrochloride is 30-120 mg/kg/day.
The general idea of the application is as follows: the inhibition effect of the dronedarone hydrochloride on the tumor cells is evaluated by carrying out dronedarone hydrochloride treatment on the digestive tract tumor cell line and observing cytotoxicity and proliferation; dronedarone hydrochloride treatment is carried out on the esophageal cancer human tumor xenograft model, animal toxicity and tumor inhibition effects are observed, and therefore the inhibition effect of dronedarone hydrochloride on the esophageal cancer human tumor xenograft model is evaluated.
In the experimental process, the optimal dronedarone hydrochloride concentration for each cell line is obtained through in vitro experiments, and the dronedarone hydrochloride is proved to be capable of strongly inhibiting the cell proliferation and anchoring independent growth of the digestive tract tumor cell line in the canceration process. Through in vivo experiments, the optimal dronedarone hydrochloride concentration for animals is obtained by screening, and the dronedarone hydrochloride can strongly inhibit the growth of the human tumor xenograft model of the esophageal cancer.
The result shows that the dronedarone hydrochloride with proper concentration has better inhibition effect on the proliferation of tumor cells and the growth of the human tumor xenograft model of the esophageal cancer, and provides a new thought and a new basis for the pharmacological action of dronedarone hydrochloride and the treatment and prevention of tumors.
Drawings
FIG. 1 shows the toxic effect of dronedarone hydrochloride on esophageal squamous cell carcinoma cells, wherein dronedarone hydrochloride has toxicity inhibition effect on esophageal squamous cell carcinoma cells KYSE150 and KYSE450 when the concentration range of dronedarone hydrochloride is 3.125-50 μ M; the figure shows the cell activity at different time points with different concentrations when the control group is 100%.
FIG. 2 shows the inhibition effect of dronedarone hydrochloride on the proliferation of esophageal squamous cell carcinoma cells, wherein dronedarone hydrochloride has the proliferation inhibition effect on esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 when the concentration range of dronedarone hydrochloride is 0-2.5 μ M; the graph shows the proliferation curves at different time points with different concentrations of the drug. P <0.05, p <0.01, p < 0.001.
FIG. 3 shows the toxic effect of dronedarone hydrochloride on gastric cancer cells, wherein dronedarone hydrochloride has toxicity inhibition effect on esophageal squamous cell carcinoma cell lines HGC27 and AGS when the concentration of dronedarone hydrochloride is 3.125-50 μ M; the figure shows the cell activity at different time points with different concentrations when the control group is 100%.
FIG. 4 shows the inhibition effect of dronedarone hydrochloride on gastric cancer cell proliferation, wherein dronedarone hydrochloride can inhibit the proliferation of gastric cell lines HGC27 and AGS when the concentration of dronedarone hydrochloride is 0-2.5. mu.M; the graph shows the proliferation curves at different time points with different concentrations of the drug. P <0.05, p <0.01, p < 0.001.
FIG. 5 shows the effect of dronedarone hydrochloride on the inhibition of the formation of esophageal squamous cell carcinoma cell clone, wherein when dronedarone hydrochloride is in the concentration range of 0 μ M-2.5 μ M, the clone number of dronedarone hydrochloride on the esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 is significantly reduced along with the increase of the dosing concentration, and the clone is significantly reduced; the figure shows the microscope photographs and statistics of the clones at different concentrations. P <0.05, p <0.01, p < 0.001.
Fig. 6 shows the effect of dronedarone hydrochloride on the growth inhibition of the esophageal cancer human tumor xenograft model, wherein the effect of dronedarone hydrochloride with different concentrations on the body weight of mice and the effect of dronedarone hydrochloride on the size, the tumor volume and the tumor weight of tumors are shown in the figure. P <0.05, p <0.01, p < 0.001.
Detailed Description
The technical solutions of the present invention are further described in detail with reference to the following examples, which are only illustrative of the present invention and should not be construed as limiting the scope of the present invention.
1. Material
1.1 Main reagents:
dronedarone hydrochloride was purchased from south-bound aerospace biotechnology limited with a purity of 97%; cell culture media was purchased from Thermo Fisher Scientific, usa; bovine fetal serum was purchased from BD, usa
1.2 main instruments and equipment:
drying CO2 Incubator, shanghai-chang scientific instruments ltd;
high speed low temperature centrifuge, Eppendorf, germany;
high content analysis imaging System In Cell Analyzer 6000, GE USA
Inverted microscope, Carl Zeiss Jena, Germany
96-well cell culture plate, Wuxi Kangsi Biotech Ltd
2. The method comprises the following steps:
2.1 cytotoxicity assay
The cell state is observed by a microscope, and the cytotoxicity experiment can be carried out when the state is good and the fusion degree reaches 80%. Washing esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 cells and gastric carcinoma cell lines HGC27 and AGS cells twice with 5ml of 1 XPBS, adding 1 ml of 0.25% trypsin digestive juice into each 10 cm culture plate, digesting for 3-5 min in a cell culture box at 37 ℃, slightly beating, and observing complete cell shedding under a microscope. Adding 5ml of complete culture medium to terminate digestion, collecting cell suspension into a 15 ml centrifuge tube, centrifuging at 1000 rpm for 3 min to discard supernatant, adding a proper amount of complete culture medium, counting by using a hemocytometer after uniform suspension, and preparing cell suspension to ensure that the cell concentration of the cell suspension reaches 12000/100 mul (KYSE 450), 8000/100 mul (KYSE 150), 6000/100 mul (HGC 27) and 8000/100 mul (AGS) and the cells are lightly blown to be uniformly distributed. Laying a 96-well plate, and adding 100 ml of cell suspension into each well to ensure that the number of cells laid into each well in the 96-well plate is 8000/100 mu l (KYSE 150), 12000/100 mu l (KYSE 450), 6000/100 mu l (HGC 27), 8000/100 mu l (AGS) (KYSE 150 cells: 10% FBS/RPMI-1640; KYSE450 cells: 10% FBS/DMEM; HGC27 cells: 10% FBS/RPMI-1640; AGS cells: 10% FBS/F12K, 37 ℃, 5% CO2) Sealing the holes around the 96-well plate with 100 μ l of 1 XPBS, and placing the culture plate at 37 ℃ and 5% CO after paving2In a cell culture incubator. After the cells are attached to the wall (0 h in the present case), the complete culture medium containing the medicine is replaced according to the setting of the medicine concentration (the medicine is firstly dissolved in DMSO and then dissolved in the culture medium according to the proportion of 1:1000, and the final concentrations of the medicine in the culture medium are 0 mu M, 3.125 mu M, 6.25 mu M, 12.5 mu M, 25 mu M and 50 mu M respectively). The drug-containing media were changed at 0 h and 24h, respectively, and the cell culture plates were removed at 24h and 48h for the corresponding time. The taken out cell culture plate is discarded the original culture medium, and is washed by 100 mul of 1 XPBSFixing the washed solution twice by using 100 mul of 4% paraformaldehyde for 30 min at room temperature, then discarding the fixed solution, adding 100 mul of 1 XPBS, washing twice, and keeping 100 mul of PBS to be placed at 4 ℃ for storage. After all the cell culture plates are fixed, each well is placed in a dark place at 37 ℃ for dyeing for 20 min by using 100 mul of DAPI (1: 3000 dilution), after dyeing is completed, the wells are washed twice by using PBS, 100 mul of PBS is reserved in each well, and the wells are placed in a dark place at 4 ℃. Finally, counting with Analyze system 6000, counting the cell number change of different drug concentration at 24h and 48h, and drawing a statistical chart, wherein the result is shown in figure 1 and figure 3.
2.2 cell proliferation assay
2.2.1 preparation of cell suspensions
After the esophageal squamous cell carcinoma cell line is taken out of the incubator, the cell state is observed by a microscope, and a cytotoxicity experiment can be carried out when the cell state is good and the fusion degree reaches 80%. The cell state was observed by microscope, and cell proliferation experiments were performed when the state was good and the degree of fusion reached 80%. Adding 1 ml of 0.25% trypsin into each 10 cm culture plate, digesting for 3-5 min in a cell culture box at 37 ℃, slightly beating, and observing complete cell shedding under a microscope. Adding 5ml of complete culture medium to terminate digestion, collecting cell suspension into a 15 ml centrifuge tube, centrifuging at 1000 rpm for 3 min, discarding supernatant, adding an appropriate amount of 1640 complete culture medium, uniformly suspending, counting by using a blood counting cell counting plate, preparing cell suspension, enabling the cell concentration of the cell suspension to reach 5000/100 mu l (KYSE 450) and 3000/100 mu l (KYSE 150), and lightly blowing and beating until the cell distribution is uniform.
2.2.2 inoculation of cells
Laying a 96-well plate, and adding 100 mul of cell suspension into each well to ensure that the number of cells in each well of the 96-well plate is about 3000/100 mul (KYSE 150), 5000/100 mul (KYSE 450), 3000/100 mul (HGC 27), 3000/100 mul (AGS), (KYSE 150: 10% FBS/RPMI-1640; KYSE 450: 10% FBS/DMEM; HGC 27: 10% FBS/RPMI-1640; AGS: 10% FBS/F12K, 37 ℃, 5% CO 1640)2) Setting 5 multiple holes for each drug concentration substance, sealing the holes around a 96-hole plate by using 100 mu l of 1 XPBS (phosphate buffer solution), placing the culture plate at 37 ℃ after paving, and placing 5% CO2In a cell culture incubator. Cell plating 16-18h adherence, marking as 0 h after cell adherence, setting each 24h as 1 experiment period, so changing the dosing culture medium (final concentrations of the drugs in the culture medium are respectively 0 mu M, 1 mu M, 1.5 mu M, 2 mu M and 2.5 mu M) every 24h and fixing the culture plate for corresponding time until 96 h, finally obtaining the culture plates with dosing of 0, 24, 48, 72 and 96 h, and ending the experiment.
2.2.3 fixation and staining of cells
And (3) discarding the original culture medium of the taken cell culture plate, firstly cleaning twice with 100 mul of 1 XPBS (phosphate buffered saline), fixing for 30 min at room temperature with 100 mul of 4% paraformaldehyde, then discarding, adding 100 mul of 1 XPBS, washing twice, and keeping 100 mul of PBS to be stored at 4 ℃. After all the cell culture plates are fixed, each well is placed in a dark place at 37 ℃ for dyeing for 20 min by using 100 mul of DAPI (1: 3000), and after dyeing is completed, the wells are washed twice by using 1 XPBS and kept by using 100 mul of PBS in each well and are placed in a dark place at 4 ℃.
2.2.4 statistics of results
The stained 96-well cell culture plate was counted in a high content analyzer and the change in the number of cells per 24h was counted, and a statistical chart was drawn, and the results are shown in fig. 2 and 4.
2.3 Soft agar colony formation assay
Experimental article: 10 mul, 200 mul, 1 ml of gun head, a plurality of 15 ml centrifuge tubes, a plurality of 250 ml glass bottles and a plurality of 1.5 ml EP tubes (all the above items need autoclaving). Fetal bovine serum, culture medium, BME, boiled agar gel, water bath pan with constant temperature of 45 ℃.
2.3.1 reagent preparation
After being prepared, 2 XBME is put into a water bath kettle at the temperature of 45 ℃ for preheating, and the formula is as follows:
after the solute is completely dissolved, the pH is adjusted to 7.4, the volume is adjusted to 500ml, and the solution is sealed and stored at 4 ℃.2 xBME must be used after sterilization with 0.22 μ M filters in a sterile environment before use.
Preparing lower layer glue:
after the addition of other reagents except agarose gel is finished, the gel can be added after 20 min of water bath.
Preparation of 10% FBS-BME:
2.3.2 Experimental procedures
Mixing the medicated lower layer glue (with drug concentration of 0, 1 μ M, 1.5 μ M, 2 μ M, 2.5 μ M) uniformly, suspending, closing the blower, spreading 3 ml of the medicated lower layer glue into 6-well plate, and arranging two multiple wells for each concentration. After paving, standing at room temperature for 1 h. Taking the cells out of the incubator, washing the cells twice with 5ml of 1 XPBS, adding 1 ml of 0.25% trypsin, digesting the cells in the incubator at 37 ℃ for 3-5 min, gently beating the cells, and observing the cells to completely shed under a microscope. The digestion was stopped by adding 5ml of complete medium, the cell suspension was collected into a 15 ml centrifuge tube, centrifuged at 1000 rpm for 3 min and the supernatant discarded before resuspension in 10% PBS-BME. After counting by adopting a blood counting plate, the concentration of the mixture is prepared to be 2.4 multiplied by 104Cell suspension of individual/ml. Spreading an upper layer of glue, putting 2.4 ml of the lower layer of glue and 1.2 ml of cell suspension into a 15 ml centrifuge tube, adding medicines with different concentrations (the medicine concentration in the upper layer of glue is 0, 1 mu M, 1.5 mu M, 2 mu M and 2.5 mu M in sequence), fully and uniformly mixing, putting into water at 60 ℃, spreading into a 6-hole plate according to 1 ml of each hole after uniformly mixing, ensuring that about 8000 cells in each hole are added into the glue, standing the 6-hole culture plate for 2 hours at room temperature, and putting into an incubator after the glue is completely solidified. And (5) observing the growth condition of the clone every day, taking a picture under a microscope for about 2 weeks, and counting the result.
2.4 establishment of human tumor xenograft model
Fresh esophageal cancer tumor tissues (patients are from tumor hospitals in Henan province, male, 46 years old, medical record number 2042083, staging T2N0M0 II, and middle-stage squamous cell carcinoma) are discarded from necrotic tissues, cut into about 3 cubic millimeters in diameter, and stuffed into the dorsal subcutaneous parts of Cb-17SCID immunodeficiency female mice of 6-7 weeks old and about 18 g. Mice were housed in a mouse SPF barrier system. After the tumor formation is about 15mm, the subcutaneous tumor is removed aseptically, solid mass is selected, the material is obtained and cut into 3 cubic millimeters small blocks, and the small blocks are transplanted to another mouse. The mice were sacrificed by dislocation of cervical vertebrae, the skin around the mice was sterilized with 75% alcohol, a small opening was punctured with a drug-dissolving needle, and the tumor tissues taken out were placed under the skin of the mice after being spread with forceps.
When the growth state of the mice is normal, dividing the tumor-bearing mice into 3 groups randomly, wherein the first group is a control group (40% polyethylene glycol +60% normal saline), the second group is a dronedarone hydrochloride low-dose group (30 mg/kg dronedarone hydrochloride is dissolved in 40% polyethylene glycol +60% normal saline), the third group is a dronedarone hydrochloride high-dose group (120 mg/kg dronedarone hydrochloride is dissolved in 40% polyethylene glycol +60% normal saline), the stomach is perfused every day according to the group, the weighing is carried out once every 5 days, the tumor volume is measured, and the tumor volume is = (long diameter x short diameter)/2. When the tumor tissue of the control group mouse reaches 1000 mm3At this time, the experiment was terminated, tumor tissue was removed, and tumor weight was weighed and recorded by photography.
3. Results
1) The toxic effect of dronedarone hydrochloride on esophageal squamous cell carcinoma cells (see figure 1), wherein when the concentration of dronedarone hydrochloride is in a range of 3.125-50 mu M, dronedarone hydrochloride has toxic inhibition effect on esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450, and the toxicity on cells is increased along with the increase of the concentration.
2) The inhibitor is the inhibition effect of dronedarone hydrochloride on the proliferation of esophageal squamous cell carcinoma cells (see figure 2), wherein when the concentration of dronedarone hydrochloride is in the range of 0 mu M-2.5 mu M, dronedarone hydrochloride can inhibit the proliferation of esophageal squamous cell carcinoma cells KYSE150 and KYSE 450; and the cell proliferation inhibition is more obvious along with the increase of the concentration of the medicine. Specifically, the dronedarone hydrochloride has obvious proliferation inhibition effect on esophageal squamous carcinoma cell lines KYSE150 and KYSE450 after 72 hours of culture when the concentration is 1-2.5 muM, wherein p is less than 0.05, p is less than 0.01, and p is less than 0.001.
3) Is the toxic effect of the dronedarone hydrochloride on gastric cancer cells (see figure 3), wherein when the concentration of the dronedarone hydrochloride ranges from 3.125 mu M to 50 mu M, the dronedarone hydrochloride has toxic inhibition effect on the esophageal squamous carcinoma cell line HGC27 and AGS; with increasing concentration, dronedarone hydrochloride has a stronger toxic effect on gastric cancer cells.
4) The inhibition effect of dronedarone hydrochloride on gastric cancer cell proliferation is shown in figure 4, wherein when the concentration range of dronedarone hydrochloride is 0-2.5 mu M, dronedarone hydrochloride can inhibit the proliferation of gastric cell lines HGC27 and AGS; and the cell proliferation inhibition is more obvious along with the increase of the concentration of the medicine. Specifically, dronedarone hydrochloride at a concentration of 1 μ M to 2.5 μ M had a significant inhibitory effect on the proliferation of gastric cancer cells HGC27 and AGS after 72 hours of culture, p <0.05, > p <0.01, > p < 0.001.
5) The effect of dronedarone hydrochloride on inhibiting the cloning formation of esophageal squamous cell carcinoma cells is achieved (see figure 5), wherein when the concentration of dronedarone hydrochloride ranges from 0 mu M to 2.5 mu M, the cloning number of dronedarone hydrochloride on the esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 is obviously reduced along with the increase of the medicine adding concentration, and the cloning is obviously reduced; the figure shows the microscope photographs and statistics of the clones at different concentrations. P <0.05, p <0.01, p < 0.001. Namely, dronedarone hydrochloride has a significant effect of inhibiting the clone number of KYSE150 at a concentration of 1 to 2.5. mu.M, and has a significant effect of inhibiting the clone number of KYSE450 at a concentration of 1.5 to 2.5. mu.M.
6) The tumor growth inhibition effect of dronedarone hydrochloride on the esophageal cancer human tumor xenograft model is shown in figure 6, wherein the body weight of a mouse treated by dronedarone hydrochloride has no obvious change compared with a control, so that the dronedarone hydrochloride has no obvious toxic or side effect on the mouse, but the tumor size, weight and tumor volume of the mouse in low-dose and high-dose groups treated by dronedarone hydrochloride are obviously reduced, so that the good tumor inhibition effect of dronedarone hydrochloride on tumors is shown. Specifically, dronedarone hydrochloride in the low dose group (30 mg/kg) and the high dose group (120 mg/kg) has significant inhibitory effects on tumor volume and tumor weight average, p is less than 0.05, p is less than 0.01, p is less than 0.001, and thus dronedarone hydrochloride can inhibit the growth of mouse tumors in the human esophageal squamous cell carcinoma transplantation tumor model at the concentration of 30 mg/kg/day to 120 mg/kg/day.
The above embodiments are only for illustrating the preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention within the knowledge of those skilled in the art should be considered as the protection scope of the present application.
Claims (9)
1. The application of dronedarone hydrochloride in preparing the medicine for resisting digestive tract tumors is characterized in that the anti-tumor medicine is a medicine for treating esophageal cancer or gastric cancer.
2. The use as claimed in claim 1 wherein the use of dronedarone hydrochloride for the manufacture of a medicament for the inhibition of the growth and transformation of esophageal squamous carcinoma cells.
3. The use according to claim 2, wherein dronedarone hydrochloride is capable of inhibiting the proliferation of esophageal squamous carcinoma cells and the number and size of colony formation at a concentration of 1 μ M to 2.5 μ M.
4. The use as claimed in claim 3 wherein the esophageal squamous cancer cells are KYSE150 cells and/or KYSE450 cells.
5. The use as claimed in claim 1 wherein the use of dronedarone hydrochloride for the manufacture of a medicament for inhibiting the growth and transformation of gastric cancer cells.
6. The use according to claim 5, wherein dronedarone hydrochloride is capable of inhibiting the proliferation and transformation of gastric cancer cells at a concentration of 1 μ M to 2.5 μ M.
7. The use according to claim 6, wherein the gastric cancer cells are HGC27 cells and/or AGS cells.
8. The use as claimed in claim 1 wherein the use of dronedarone hydrochloride for the manufacture of a medicament for inhibiting the growth of mouse tumours in a human model of oesophageal squamous carcinoma transplantable tumours.
9. The use as claimed in claim 8 wherein dronedarone hydrochloride is capable of inhibiting the growth of mouse tumours in a human derived oesophageal squamous carcinoma graft tumour model at a concentration of 30 mg/kg/day to 120 mg/kg/day.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112618535A (en) * | 2020-12-30 | 2021-04-09 | 中山大学附属第六医院 | Application of dronedarone in preparation of medicine for preventing and treating colitis |
| WO2023092943A1 (en) * | 2021-11-23 | 2023-06-01 | 中国人民解放军陆军军医大学第一附属医院 | Use of dronedarone hydrochloride in combination with 5-fluorouracil in preparation of anti-tumor drug |
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| ELLIOTT, MITCHELL J.; JERZAK, KATARZYNA J.; COCKBURN, JESSICA G.: "The Antiarrhythmic Drug, Dronedarone, Demonstrates Cytotoxic Effects in Breast Cancer Independent of Thyroid Hormone Receptor Alpha 1 (THR alpha 1) Antagonism", 《SCIENTIFIC REPORTS》 * |
| T. A. MELÉNDEZ, A等: "Dronedarone blockage of the tumor-related Kv10.1 channel: a comparison with amiodarone", 《PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY》 * |
| 朱少平等: "盐酸胺碘酮对人食管癌细胞EC9706增殖的影响", 《医药导报》 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112618535A (en) * | 2020-12-30 | 2021-04-09 | 中山大学附属第六医院 | Application of dronedarone in preparation of medicine for preventing and treating colitis |
| CN112618535B (en) * | 2020-12-30 | 2022-04-12 | 中山大学附属第六医院 | Application of dronedarone in preparation of medicine for preventing and treating colitis |
| WO2023092943A1 (en) * | 2021-11-23 | 2023-06-01 | 中国人民解放军陆军军医大学第一附属医院 | Use of dronedarone hydrochloride in combination with 5-fluorouracil in preparation of anti-tumor drug |
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