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Application of MAPK14 inhibitor in preparation of drug

A technology for preparing drugs and inhibitors, applied in the field of biomedicine, can solve the problems of lack of therapeutic drugs, incompletely clear pathogenesis of prolactin adenoma, and few clinical therapeutic targets.

Active Publication Date: 2020-06-19
王雄 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the pathogenesis of prolactinoma is not completely clear, there are few clinical therapeutic targets and there is a lack of therapeutic drugs, so it is urgent to find new targets and drugs for the treatment of prolactinoma

Method used

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  • Application of MAPK14 inhibitor in preparation of drug
  • Application of MAPK14 inhibitor in preparation of drug
  • Application of MAPK14 inhibitor in preparation of drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] MAPK14 knockout inhibits estradiol-induced mouse prolactinoma growth and PRL secretion

[0089] 1.1. Establishment of mouse prolactinoma model

[0090] Twenty C57 mice were randomly divided into normal group and model group, 10 in each group; the other group was MAPK14 knockout (MAPK14(- / -)) mice group, 10.

[0091] The model group mice and MAPK14(- / -) mice were intraperitoneally injected with estradiol benzoate injection at a dose of 20 mg / kg, once every 4 days for 32 days; the normal group was not treated.

[0092] 1.2. Collection of samples

[0093] After 32 days of estrogen injection, the mice were fasted for 12 hours and had free access to water. On the next morning, blood was collected from the fundus venous plexus of mice in the normal group, the model group and the MAPK14(- / -) group, and the serum was collected by centrifugation for detection. After the mice were sacrificed, the pituitary glands were removed and placed at -80°C for use.

[0094] 1.3. Immunof...

Embodiment 2

[0106] Knockout of MAPK14 inhibits prolactinoma growth and PRL secretion in DRD2 knockout mice

[0107] 2.1. Animal grouping

[0108] Mice were divided into 3 groups: C57 normal mice as normal group, DRD2 gene knockout (DRD2(- / -)) mice group, MAPK14(- / -) mice and DRD2(- / -) mice Hybrid offspring MAPK14(- / -)*DRD2(- / -) mouse group. DRD2(- / -) mice are prolactinoma model mice.

[0109] 2.2. Sample collection

[0110] The mice were fasted for 12 h and had free access to water. On the next morning, blood was collected from the fundus venous plexus of mice in the normal group, DRD2(- / -) group and MAPK14(- / -)*DRD2(- / -) group, and the serum was centrifuged for detection. After the mice were sacrificed, the pituitary glands were removed.

[0111] 2.3. Analysis results of the ratio of pituitary tumor weight to body weight

[0112] Weigh the body weight of mice in normal group, DRD2(- / -) group and MAPK14(- / -)*DRD2(- / -) group and the weight of pituitary tumor, and calculate the ratio ...

Embodiment 3

[0122] MAPK14 gene silencing reduces PRL production in pituitary tumor GH3 cells

[0123] 3.1 Design of MAPK14-siRNA

[0124] The sequence of MAPK14-siRNA is as follows:

[0125] MAPK14-siRNA1: GGTCCCTGGAGGAATTCAA (SEQ ID NO: 1);

[0126] MAPK14-siRNA2: CCGAAGATGAACTTCGCAA (SEQ ID NO: 2);

[0127] MAPK14-siRNA3: GGACCTCTTATAGACGAA (SEQ ID NO: 3).

[0128] 3.2. Cell grouping

[0129] GH3 cells were divided into: blank group, negative control (NC) group, MAPK14-siRNA1 (30nM) group, MAPK14-siRNA1 (50nM) group, MAPK14-siRNA1 (100nM) group, MAPK14-siRNA2 (30nM) group, MAPK14-siRNA2 (50nM) group, MAPK14-siRNA2(100nM) group, MAPK14-siRNA3(30nM) group, MAPK14-siRNA3(50nM) group, MAPK14-siRNA3(100nM) group.

[0130] 3.3. RT-qPCR analysis

[0131] After GH3 cells were plated for 24 hours, each group was transfected with siRNA according to the siRNA transfection instructions, and RNA was extracted 48 hours after transfection. RT-qPCR was used to detect the expression of MAPK14 and...

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Abstract

The invention provides application of an MAPK14 inhibitor in preparation of a drug. The drug is used for at least one of the following steps of: inhibiting generation of PRL; inhibiting secretion of PRL; inhibiting growth of pituitary prolactin adenoma. MAPK14 promotes growth of pituitary prolactin adenoma and secretion of PRL, and growth of pituitary prolactin adenoma and secretion of PRL can beremarkably inhibited by inhibiting or knocking out an MAPK14 gene. Therefore, MAPK14 can be used as a new therapeutic target of prolactin adenoma, and the MAPK14 inhibitor can be used for preparing adrug for preventing or treating prolactin adenoma. The co-localization phenomenon of MAPK14 and PRL proteins in the pituitary tissue of a patient with pituitary prolactin adenoma is remarkable, and the expression of MAPK14 and PRL proteins in the pituitary tissue of the patient with pituitary prolactin is remarkably increased. Therefore, the MAPK14 gene can be used as a prolactin adenoma diagnostic marker for diagnosing prolactin adenoma.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to the application of MAPK14 inhibitors in the preparation of drugs, the use of MAPK14 gene as a diagnostic marker for prolactinomas, the method for screening drugs, the application of reagents in the preparation of kits and the regulation of prolactin glands methods for tumor cell proliferation. Background technique [0002] Pituitary tumor is one of the common benign intracranial tumors. Its incidence rate is second only to glioma and meningioma in intracranial tumors, accounting for about 10% of intracranial tumors. The rate has been increasing year by year. As the tumor continues to grow, it can compress the surrounding structures of the sella region, such as the optic nerve, cavernous sinus, base of the brain artery, hypothalamus, etc., and even involve the frontal lobe and brainstem, resulting in severe dysfunction. At the same time, tumor growth can also lead to disorders...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P35/00A61K31/713A61K48/00
CPCA61K45/00A61P35/00A61K31/713A61K48/005
Inventor 王雄丁巧燕吴金虎
Owner 王雄