CN115317483A - Application of chloroquine and derivatives thereof in preparation of PGCCs (PGCCs) inhibitor - Google Patents
Application of chloroquine and derivatives thereof in preparation of PGCCs (PGCCs) inhibitor Download PDFInfo
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Abstract
The invention belongs to the field of biological medicines, and discloses application of chloroquine and derivatives thereof in preparation of PGCCs (PGCCs) inhibitors. The PGCCs inhibitor prepared from chloroquine and derivatives thereof is used in combination with basic chemotherapeutic drugs such as paclitaxel or cisplatin and the like, can inhibit the formation of dormant polyploid giant tumor cells after conventional treatment, and further inhibit the recurrence and metastasis of nasopharyngeal carcinoma, thereby improving the survival rate of patients with nasopharyngeal carcinoma and the prognosis thereof, and having important clinical significance and industrial popularization and application prospects.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and relates to application of chloroquine and derivatives thereof in preparation of PGCCs (PGCCs) inhibitors, in particular to application of chloroquine and/or hydroxychloroquine in preparation of PGCCs inhibitors.
Background
Recurrence and metastasis are major causes of poor prognosis in many malignant patients. Tumor dormancy is a common clinical phenomenon, and patients often remain asymptomatic for some time after treatment. However, dormant tumors may awaken at any time and rapidly enter an explosive, rapidly growing stage, forming recurrent foci or new metastases. Tumor dormancy and awakening are important risk factors for tumor recurrence and metastasis. Polyploid giant tumor cells (PGCCs) are of interest as a special class of tumor quiescent cells. Studies have shown that treatment-induced dormancy has been shown to lead to persistent proliferation arrest, leading to the formation of PGCCs. PGCCs have significant advantages over normal cancer cells in coping with stress and reproduction. PGCCs cells have the characteristics of polyploidy (multinuclear or one large nucleus), huge volume, cell cycle retardation, rapid division of daughter cells in a non-mitotic (budding or bursting) mode after dormancy is finished and the like, and the divided daughter cells can be differentiated to terminal cells to provide rich nutrition and complex tumor microenvironment for the growth of tumor cells, so the PGCCs cells are high-risk tumor dormant cells. Currently, a specific treatment method for inhibiting recurrence and metastasis of malignant tumors and improving prognosis thereof by targeting dormant polyploid tumor cells is clinically lacked.
Disclosure of Invention
In view of the above, the invention provides an application of chloroquine and derivatives thereof in preparation of PGCCs inhibitors.
In order to achieve the above purpose, the invention provides the following technical scheme:
the invention provides application of chloroquine or pharmaceutically acceptable salt thereof in preparing PGCCs (PGCCs) inhibitor, wherein the PGCCs inhibitor is a medicament for inhibiting the generation of dormant polyploid giant tumor cells, and the chemical formula of the chloroquine is C 18 H 26 ClN 3 The molecular weight of chloroquine is 319.87, the structural formula of chloroquine is shown as the following formula,
the invention also provides application of hydroxychloroquine or pharmaceutically acceptable salts thereof in preparing PGCCs (tumor mass centers) inhibitors, wherein the PGCCs inhibitors are medicines for inhibiting the generation of the dormant polyploid giant tumor cells, and the hydroxychloroquine has a chemical formula C 18 H 26 ClN 3 O, the molecular weight of hydroxychloroquine is 335.87, the structural formula of hydroxychloroquine is shown as the following formula,
further, the PGCCs inhibitors are useful for inhibiting the production of dormant polyploid megatumor cells upon administration of chemotherapeutic agents.
Further, the chemotherapy drug is a drug for killing malignant tumor cells.
Further, the chemotherapeutic drug is cisplatin or paclitaxel.
Further, the active ingredient of the inhibitor comprises chloroquine and/or hydroxychloroquine.
The dosage form of the PGCCs inhibitor can be any dosage form suitable for clinical use, and comprises injections, capsules, tablets, pills or granules.
Further, the dosage form of the PGCCs inhibitor is injection.
Further, the active ingredient of the PGCCs inhibitor is chloroquine, and the concentration of chloroquine in the PGCCs inhibitor is 10 mu m.
Further, the active ingredient of the PGCCs inhibitor is hydroxychloroquine, and the concentration of the hydroxychloroquine in the PGCCs inhibitor is 100 mu M.
Further, the active ingredients of the PGCCs inhibitor are chloroquine and hydroxychloroquine, and the concentration of chloroquine in the PGCCs inhibitor is 10 mu M and the concentration of hydroxychloroquine in the PGCCs inhibitor is 100 mu M.
Compared with the prior art, the invention has the following technical effects:
1. in vitro experiments, chloroquine or hydroxychloroquine can inhibit the formation of huge tumor cells of the dormant polyploid.
2. The clinical highly-relevant nude mouse subcutaneous recurrence model which is successfully modeled is taken as an experimental object, and chloroquine or hydroxychloroquine is found to be capable of remarkably inhibiting the formation of dormant polyploid giant tumor cells and remarkably inhibiting the recurrence of nasopharyngeal carcinoma.
3. The successful modeling clinical highly-relevant nude mouse nasopharyngeal carcinoma in-situ metastasis model is taken as an experimental object, and the chloroquine or hydroxychloroquine is found to be capable of remarkably inhibiting the formation of dormant polyploid giant tumor cells and remarkably inhibiting the metastasis of nasopharyngeal carcinoma.
4. The chloroquine or hydroxychloroquine is used for preparing PGCCs inhibitor, and has the advantages of low cost, small drug toxicity in a safe dose range, good stability and important development and application prospects.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the prior art descriptions will be briefly described below.
FIG. 1 is the optical microscopic image of the cell morphology of control group 1, chloroquine group 1 and hydroxychloroquine group 1 at the 7 th day of the in vitro experiment;
FIG. 2 is a graph showing the change of cell activities in control group 2, chloroquine group 2 and hydroxychloroquine group 2 of in vitro experiments;
FIG. 3 is a diagram showing the experimental results of subcutaneous recurrence model of clinically highly relevant nude mice; wherein, the A picture is a line graph of the growth condition of subcutaneous tumors of a control group 3, a cis-platinum group 3, a chloroquine group 3 and a hydroxychloroquine group 3; b is a histogram of the number of dormant polyploid giant tumor cells in the subcutaneous primary tumors of the control group 3, the cis-platinum group 3, the chloroquine group 3 and the hydroxychloroquine group 3; the C picture is a line graph of the recurrence rates of a control group 3, a cis-platinum group 3, a chloroquine group 3 and a hydroxychloroquine group 3;
FIG. 4 is a schematic diagram showing the experimental results of a clinical highly-relevant nude mouse nasopharyngeal carcinoma in-situ metastasis model; wherein, the A picture is a histogram of the number of dormant polyploid giant tumor cells in the nasopharyngeal carcinoma in-situ tumors of nude mice of a control group 4, a cisplatin group 4, a chloroquine group 4 and a hydroxychloroquine group 4; the B picture is a control group 4, a cisplatin group 4, a chloroquine group 4 and a hydroxychloroquine group 4 transfer rate line graph; the C graph is a line graph of the survival rates of the control group 4, the cisplatin group 4, the chloroquine group 4 and the hydroxychloroquine group 4. And D is a line graph of the change of the body weight of the nude mice of the control group 4, the cisplatin group 4, the chloroquine group 4 and the hydroxychloroquine group 4.
Detailed Description
The invention discloses application of Chloroquine (CQ) and derivatives thereof in preparation of PGCCs inhibitors, and can be realized by appropriately improving process parameters by taking the contents of the Chloroquine (CQ) and the derivatives thereof as reference by a person skilled in the art. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations and modifications, or appropriate variations and combinations of the methods and applications described herein may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
In the present invention, all the raw materials and reagents are commercially available.
Example 1:
chloroquine was dissolved in DMSO (dimethyl sulfoxide), and diluted into 1640 medium to obtain 1640 medium with chloroquine concentration of 10 μm.
Hydroxychloroquine was dissolved in DMSO (dimethyl sulfoxide), and diluted into 1640 medium to obtain 1640 medium with hydroxychloroquine concentration of 100 μm.
Control group 1: nasopharyngeal carcinoma cell line CNE-2 was inoculated in a 6-well plate, cultured for 1 day, added with Paclitaxel (PTX) so that the concentration of PTX in the medium became 150 ng/. Mu.L, cultured for 18 hours, and then cultured for 6 days while replacing 1640 medium containing 10% FBS (fetal bovine serum).
Chloroquine group 1: the nasopharyngeal carcinoma cell line CNE-2 was inoculated in a 66-well plate, cultured for 1 day, then, chloroquine-containing 1640 medium was added, cultured for 1 day, then, paclitaxel (PTX) was added so that the concentration of PTX in the medium became 150 ng/. Mu.L, cultured for 18 hours, and then, the medium containing 10% FBS (fetal bovine serum) in 1640 was replaced, and cultured for 6 days.
Hydroxychloroquine group 1: the nasopharyngeal carcinoma cell line CNE-2 was inoculated to a 6-well plate, cultured for 1 day, then a Hydroxychloroquine-containing 1640 medium was added, cultured for 1 day, then Paclitaxel (PTX) was added so that the concentration of PTX in the medium became 150 ng/. Mu.L, cultured for 18 hours, and then the medium containing 10% FBS (fetal bovine serum) in 1640 was replaced, and cultured for 6 days.
The results of optical microscope observation of the control group 1, the chloroquine group 1 and the hydroxychloroquine group 1 are shown in fig. 1.
FIG. 1 shows that the cells of control 1 exhibited the characteristics of the dormant polyploid megatumor cells, illustrating the formation of the dormant polyploid megatumor cells in a viable state; the chloroquine group 1 and hydroxychloroquine group 1 cells failed to form dormant polyploid giant tumor cells, and all cells died.
Example 2:
chloroquine was dissolved in DMSO (dimethyl sulfoxide), and diluted into 1640 medium to obtain 1640 medium with a chloroquine concentration of 10 μm.
Hydroxychloroquine was dissolved in DMSO (dimethyl sulfoxide), and diluted into 1640 medium to obtain 1640 medium with hydroxychloroquine concentration of 100 μm.
Control group 2: nasopharyngeal carcinoma cell line CNE-2 was inoculated in a 96-well plate, cultured for 1 day, added with Paclitaxel (PTX) so that the concentration of PTX in the medium became 150 ng/. Mu.L, cultured for 18 hours, and then replaced with 1640 medium containing 10% FBS (fetal bovine serum) and cultured for 15 days.
Chloroquine group 2: the nasopharyngeal carcinoma cell line CNE-2 was inoculated in a 96-well plate, cultured for 1 day, added with a medium 1640 containing chloroquine, cultured for 1 day, added with Paclitaxel (PTX) so that the concentration of PTX in the medium became 150 ng/. Mu.L, cultured for 18 hours, and cultured for 15 days while replacing the medium 1640 containing 10% FBS (fetal bovine serum).
Hydroxychloroquine group 2: the nasopharyngeal carcinoma cell line CNE-2 was inoculated to a 96-well plate, cultured for 1 day, then a Hydroxychloroquine-containing 1640 medium was added, cultured for 1 day, then Paclitaxel (PTX) was added so that the concentration of PTX in the medium became 150 ng/. Mu.L, cultured for 18 hours, and then the medium containing 10% FBS (fetal bovine serum) in 1640 was replaced, and cultured for 15 days.
The cell activity detection is carried out on the control group 2, the chloroquine group 2 and the hydroxychloroquine group 2 by using a CCK8 reagent every day, the CCK8 reagent is mixed with a 1640 basic culture medium 1:9 to prepare a mixed solution, 100 mu l of the mixed solution is added into each hole, the mixed solution is placed in a cell incubator in a dark place to be incubated for 1 hour, and then a spectrophotometer is used for detecting an OD450 value, so that the cell activity is reflected. Each group was tested in 3 wells per day and the results are shown in figure 3.
As can be seen from fig. 2, in control group 2, the number of cells gradually decreased from day 1 to day 7, and the number of cells remained at a certain level but did not significantly change from day 7 to day 10, and gradually increased after day 10. In the chloroquine group 2 and the hydroxychloroquine group 2, the cell number gradually decreased to a lower level (much lower than the cell number level at day 7 of the control group 2, close to 0) from day 1 to day 7, and thereafter, the cell number did not increase.
The results in fig. 1 and 2 show that chloroquine and hydroxychloroquine can inhibit the formation of dormant polyploid giant tumor cells.
Example 3
Cisplatin (cissplatin) was diluted into PBS to prepare Cisplatin injection.
Dissolving chloroquine in DMSO (dimethyl sulfoxide), diluting into PBS, and adding cisplatin to obtain cisplatin/chloroquine injection, wherein the dosage ratio of cisplatin to chloroquine in the injection is 5mg:40mg.
Dissolving hydroxychloroquine in DMSO (dimethyl sulfoxide), diluting into PBS, adding cisplatin, and making into cisplatin/hydroxychloroquine injection, wherein the dosage ratio of cisplatin to hydroxychloroquine in the injection is 5mg:40mg.
Control group 3: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Subcutaneously planting 5X 10 in the interscapular region of each nude mouse 6 The number of luciferase-labeled CNE-2 cells was monitored every 72 hours for changes in tumor size in mice with a vernier caliper. Drug treatment was started on day 5 post tumor inoculation, with 200 μ Ι _ of PBS per intraperitoneal injection, twice weekly for up to day 25. Mice were deeply anesthetized with chloral hydrate (4% solution, 400 mg/kg) and an incision was made 1cm above the tumor floor, followed by suturing the incision after gently digging out the tumor tissue. To confirm that no primary tumor cells remained, whole-body BLI imaging (bioluminescence imaging) was performed. After the primary tumor was excised, the recurrence of tumor in nude mice was observed every two days, and the size change of the tumor in mice was monitored with a vernier caliper.
Cis-platinum group 3: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Subcutaneously planting 5X 10 in the interscapular region of each nude mouse 6 The number of luciferase-labeled CNE-2 cells was monitored every 72 hours for changes in tumor size in mice with a vernier caliper. The drug treatment is started on the 5 th day after tumor inoculation, and each nude mouse is injected with cisplatin injection in the abdominal cavity at the dose of 5mg/kg twice a week for the period of 25 th day. With chloral hydrate (4%Solution, 400 mg/kg) mice were deeply anesthetized and an incision was made 1cm above the tumor floor, gently digging out tumor tissue and suturing the incision. To confirm that no primary tumor cells remained, whole-body BLI imaging (bioluminescence imaging) was performed. After the primary tumor was excised, the recurrence of the tumor in nude mice was observed every two days, and the size change of the tumor in mice was monitored with a vernier caliper.
Chloroquine group 3: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Subcutaneously planting 5X 10 in the interscapular region of each nude mouse 6 The number of luciferase-labeled CNE-2 cells was monitored every 72 hours for changes in tumor size in mice with a vernier caliper. On the fourth day after tumor inoculation, 40mg/kg of chloroquine is injected into the abdominal cavity of each nude mouse, the drug treatment is started on the 5 th day after tumor inoculation, and cisplatin/chloroquine injection (the injection dosage is 5mg/kg of cisplatin and 40mg/kg of chloroquine) is injected into the abdominal cavity of each nude mouse twice a week and lasts until the 25 th day. Mice were deeply anesthetized with chloral hydrate (4% solution, 400 mg/kg) and an incision was made 1cm above the tumor floor, followed by suturing the incision after gently digging out the tumor tissue. To confirm that no residual primary tumor cells remained, whole-body BLI imaging (bioluminescence imaging) was performed. After the primary tumor was excised, the recurrence of the tumor in nude mice was observed every two days, and the size change of the tumor in mice was monitored with a vernier caliper.
Hydroxychloroquine group 3: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Subcutaneously planting 5X 10 in the interscapular region of each nude mouse 6 The number of CNE-2 cells labeled with luciferase was monitored every 72 hours for changes in tumor size in mice with a vernier caliper. On the fourth day after tumor inoculation, hydroxychloroquine is injected into the abdominal cavity of each nude mouse at a dose of 40mg/kg, drug treatment is started on the 5 th day after tumor inoculation, and cisplatin/hydroxychloroquine injection (the injection dose is 5mg/kg of cisplatin and 40mg/kg of hydroxychloroquine) is injected into the abdominal cavity of each nude mouse at a time, twice a week and continuously till the 25 th day. Mice were deeply anesthetized with chloral hydrate (4% solution, 400 mg/kg) and an incision was made 1cm above the tumor floor, followed by suturing the incision after gently digging out the tumor tissue. To confirm that no residual primary tumor cells remained, whole-body BLI imaging (bioluminescence imaging) was performed. Primary swelling of hairAfter tumor excision, the mice were observed for tumor recurrence every two days, and the change in size of the tumor that recurs was monitored with a vernier caliper.
All primary tumors of the four groups were embedded in paraffin and HE stained, and the number of PGCC cells in the sections was counted.
FIG. 3 is a diagram showing the experimental results of subcutaneous recurrence model of clinically highly relevant nude mice.
In panel A of FIG. 3, the upper left panel shows the growth of primary and recurrent tumors in the control group 3, the upper right panel shows the growth of primary and recurrent tumors in the cisplatin group 3, the lower left panel shows the growth of primary and recurrent tumors in the chloroquine group 3, and the lower right panel shows the growth of primary and recurrent tumors in the hydroxychloroquine group 3. As can be seen from the graph of fig. 3A, the control group 3 tumors grew the fastest and the most recurrent tumors grew, and the chloroquine group 3 and hydroxychloroquine group 3 tumors grew significantly slower and fewer mice grew recurrent tumors than the control group 3 and cisplatin group 3.
FIG. 3B is a bar graph showing the number of dormant polyploid megatumor cells in the subcutaneous primary tumors of control group 3, cisplatin group 3, chloroquine group 3, and hydroxychloroquine group 3. As can be seen from the graph of fig. 3B, the number of dormant polyploid megatumor cells was the greatest in the cisplatin group 3, and the number of dormant polyploid megatumor cells was significantly reduced in the chloroquine group 3 and the hydroxychloroquine group 3, compared to the other two groups.
The recurrence rates of control group 3, cisplatin group 3, chloroquine group 3, and hydroxychloroquine group 3 were calculated, and the results are shown in fig. 3, panel C.
Recurrence rate = number of relapsed nude mice/total number of nude mice 100%.
As can be seen from the C-chart of FIG. 3, the control group 3 had the highest recurrence rate, and the chloroquine group 3 and hydroxychloroquine group 3 had lower recurrence rates than the other two groups.
Example 4
Cisplatin (cissplatin) was diluted into PBS to prepare Cisplatin injection.
Dissolving chloroquine in DMSO (dimethyl sulfoxide), diluting into PBS, and adding cisplatin to obtain cisplatin/chloroquine injection, wherein the dosage ratio of cisplatin to chloroquine in the injection is 5mg:40mg.
Dissolving hydroxychloroquine in DMSO (dimethyl sulfoxide), diluting into PBS, adding cisplatin, and making into cisplatin/hydroxychloroquine injection, wherein the dosage ratio of cisplatin to hydroxychloroquine in the injection is 5mg:40mg.
Control group 4: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Deep anesthesia was performed with chloral hydrate (4% solution, 400 mg/kg) and placed in a stereotactic frame in the supine position. The mouth was opened, the tongue was pulled aside with a curved forceps, and then the contents were injected into a 1mL sterile syringe containing 2X 10 6 50 μ L of cell suspension of individual luciferase-labeled CNE-2 cells was injected into the junction of the soft and hard palate. Drug treatment was started on day 5 after tumor inoculation, with 200 μ L of PBS per intraperitoneal injection, twice a week.
Cis-platinum group 4: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Deep anesthesia was performed with chloral hydrate (4% solution, 400 mg/kg) and placed in a stereotactic frame in the supine position. The mouth was opened, the tongue was pulled aside with a curved forceps, and then the contents were injected into a 1mL sterile syringe containing 2X 10 6 50 μ L of cell suspension of individual luciferase-labeled CNE-2 cells was injected into the junction of the soft and hard palate. The drug treatment is started 5 days after tumor inoculation, and cisplatin injection is injected into the abdominal cavity of each nude mouse at the dose of 5mg/kg twice a week.
Chloroquine group 4: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Deep anesthesia was performed with chloral hydrate (4% solution, 400 mg/kg) and placed in a stereotactic frame in the supine position. The mouth was opened, the tongue was pulled aside with a curved forceps, and the contents of 2X 10 were filled with a 1mL sterile syringe 6 50 μ L of cell suspension of individual luciferase-labeled CNE-2 cells was injected into the junction of the soft and hard palate. On the fourth day after tumor inoculation, 40mg/kg of chloroquine is injected into the abdominal cavity of each nude mouse, the drug treatment is started on the 5 th day after tumor inoculation, and cisplatin/chloroquine injection (the injection dosage is 5mg/kg of cisplatin and 40mg/kg of chloroquine) is injected into the abdominal cavity of each nude mouse twice a week.
Hydroxychloroquine group 4: BALB/c nude mice, male, 6 weeks old, body weight 20 + -5 g. Deep anesthesia was performed with chloral hydrate (4% solution, 400 mg/kg) and placed in a stereotactic frame in the supine position. The mouth is opened, the tongue is pulled aside by a curved forceps, and thenThen using a 1mL sterile syringe to contain 2X 10 6 50 μ L of cell suspension of individual luciferase-labeled CNE-2 cells was injected into the junction of the soft and hard palate. On the fourth day after tumor inoculation, hydroxychloroquine is injected into the abdominal cavity of each nude mouse at a dose of 40mg/kg, and drug treatment is started on the 5 th day after tumor inoculation, and cisplatin/hydroxychloroquine injection (the injection dose is 5mg/kg of cisplatin and 40mg/kg of hydroxychloroquine) is injected into the abdominal cavity of each nude mouse at a time and is injected twice per week.
The body weight of each group of nude mice was measured every other day.
Whole-body BLI imaging (bioluminescent imaging) was used to detect growth of tumors in situ and metastasis away from the site of nasopharyngeal carcinoma. After death of the nude mice, the in situ tumors were embedded in paraffin and immunohistochemically stained, and the number of PGCC cells in the sections was counted.
FIG. 4 is a schematic diagram showing the experimental results of the in situ metastasis model of nasopharyngeal carcinoma in nude mice with high clinical relevance.
FIG. 4 is a graph A showing the numbers of dormant polyploid megatumor cells in the nasopharyngeal carcinoma orthotopic tumors of nude mice of control group 4, cisplatin group 4, chloroquine group 4, and hydroxychloroquine group 4. The number of dormant polyploid huge tumor cells was the most in the cis-platinum group 4, and the number of dormant polyploid huge tumor cells was significantly reduced in the chloroquine group 4 and hydroxychloroquine group 4 as compared with the other two groups.
FIG. 4 is a B-plot showing the transfer rates of control group 4, cisplatin group 4, chloroquine group 4, and hydroxychloroquine group 4; the transfer rate of the control group 4 is the highest, and the transfer rates of the chloroquine group 4 and the hydroxychloroquine group 4 are obviously reduced.
FIG. 4 is a C-plot showing the survival rates of control group 4, cisplatin group 4, chloroquine group 4, and hydroxychloroquine group 4; the control group 4 has the lowest survival rate and the worst prognosis, while the chloroquine group 4 and the hydroxychloroquine group 4 have the obviously improved survival rate and the obviously improved prognosis.
FIG. 4 is a graph D showing the line graphs of the body weight changes of nude mice in the control group 4, cisplatin group 4, chloroquine group 4, and hydroxychloroquine group 4. The body weight of the nude mice in the cis-platinum group 4 is slightly reduced compared with that of the nude mice in the control group 4, while the body weight of the nude mice in the chloroquine group 4 and the hydroxychloroquine group 4 is not statistically different from that of the nude mice in the cis-platinum group 4.
The results in figure 4 show that chloroquine and hydroxychloroquine can obviously inhibit the formation of huge tumor cells of the dormant polyploid, obviously inhibit the transfer of nasopharyngeal carcinoma and obviously improve the survival rate of the model nude mice. The chloroquine and the hydroxychloroquine are used for preparing the medicine for treating the nasopharyngeal carcinoma, and the medicine toxicity is low.
The above-described embodiments are merely preferred embodiments of the present invention, which should not be construed as limiting the invention, and any modifications, equivalents, improvements, etc. made without departing from the basic principles of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. Application of chloroquine or pharmaceutically acceptable salt thereof in preparation of PGCCs (receptor ligands for cell proliferation) inhibitor, wherein the PGCCs inhibitor is a medicament for inhibiting generation of dormant polyploid giant tumor cells, and the chemical formula of the chloroquine is C 18 H 26 ClN 3 The molecular weight of chloroquine is 319.87, the structural formula of chloroquine is shown as the following formula,
2. application of hydroxychloroquine or pharmaceutically acceptable salt thereof in preparation of PGCCs inhibitor, wherein the PGCCs inhibitor is used for inhibiting generation of dormant polyploid megatumor cells, and the chemical formula of hydroxychloroquine is C 18 H 26 ClN 3 O, the molecular weight of hydroxychloroquine is 335.87, the structural formula of hydroxychloroquine is shown as the following formula,
3. the use of claim 1 or 2, wherein the PGCCs inhibitor is for use in inhibiting the production of quiescent polyploid megatumor cells when chemotherapeutic agents are used.
4. The use of claim 3, wherein the chemotherapeutic agent is an agent for killing malignant cells.
5. The use of claim 3, wherein the chemotherapeutic agent is cisplatin or paclitaxel.
6. A PGCCs inhibitor, wherein the active ingredient of the PGCCs inhibitor comprises chloroquine and/or hydroxychloroquine.
7. The PGCCs inhibitor according to claim 6, wherein the dosage form of the PGCCs inhibitor is an injection.
8. The PGCCs inhibitor according to claim 7, wherein the active ingredient of the PGCCs inhibitor is chloroquine, and the concentration of chloroquine in the PGCCs inhibitor is 10 μ Μ.
9. The PGCCs inhibitor according to claim 7, wherein the active ingredient of the PGCCs inhibitor is hydroxychloroquine, and the concentration of hydroxychloroquine in the PGCCs inhibitor is 100 μ M.
10. The PGCCs inhibitor according to claim 7, wherein the active ingredients of the PGCCs inhibitor are chloroquine and hydroxychloroquine, and the concentration of chloroquine in the PGCCs inhibitor is 10 μ Μ and the concentration of hydroxychloroquine is 100 μ Μ.
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