CN106265631A - Biochanin A purposes in preparation suppression breast carcinoma propagation, diversion medicaments and mammary cancer chemotherapy sensitizer - Google Patents

Biochanin A purposes in preparation suppression breast carcinoma propagation, diversion medicaments and mammary cancer chemotherapy sensitizer Download PDF

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Publication number
CN106265631A
CN106265631A CN201610902969.7A CN201610902969A CN106265631A CN 106265631 A CN106265631 A CN 106265631A CN 201610902969 A CN201610902969 A CN 201610902969A CN 106265631 A CN106265631 A CN 106265631A
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China
Prior art keywords
biochanin
breast carcinoma
purposes
propagation
zeb1
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CN201610902969.7A
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Chinese (zh)
Inventor
杨爽
张震
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Nankai University
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Nankai University
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Priority to CN201610902969.7A priority Critical patent/CN106265631A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides Biochanin A (Biochanin A) and at preparation suppression breast carcinoma propagation, the medicine of transfer and prepare the purposes in mammary cancer chemotherapy sensitizer.The compound that the present invention relates to has and reduces the effect of ZEB1 gene expression in breast carcinoma, and and then the suppression propagation of breast carcinoma, transfer and chemotherapy resistance, show stronger breast cancer inhibition effect and Chemosensitizing effect, thus for the new strategy of breast cancer treatment offer.

Description

Biochanin A is at preparation suppression breast carcinoma propagation, diversion medicaments and mammary cancer chemotherapy Purposes in sensitizer
Technical field
The invention provides the new application of Biochanin A (Biochanin A), relate to Biochanin A (Biochanin A) is at the table of preparation suppression ZEB1 (zinc refer to-containing homology frame transcription regulaton factor delta-globulin enhancer 1) Reach, and then suppress the propagation of breast carcinoma, the medicine of transfer and prepare the application in mammary cancer chemotherapy sensitizer, belong to biological doctor Medicine field.
Background technology
Breast carcinoma occupies the first place of female malignant sickness rate the most in the world, and it is dead to become female malignant The one of the main reasons died.Although the treatment of breast carcinoma has been obtained for significant progress, but still has many patients to die from The chemotherapy resistance of breast carcinoma, recur and recur the transfer brought.
Numerous researchs show, ZEB1 plays an important role in propagation, transfer and the chemotherapy resistance of breast carcinoma, but Now still without the inhibitor of ZEB1.Therefore, the inhibitor of exploitation ZEB1, as a new target spot, mammary gland can be given The treatment of cancer provides new strategy.
A kind of natural extract compound of Biochanin A (Biochanin A), is mainly derived from leguminous plant chickpea kind The germ fraction of son, Herba Trifolii Pratentis herb etc..
Summary of the invention
The problem that the purpose of the present invention solves how to suppress ZEB1 to express, it is provided that a kind of Biochanin A (Biochanin A) new application, i.e. Biochanin A are in the expression of preparation suppression ZEB1, and then the suppression propagation of breast carcinoma, the medicine of transfer And prepare the application in chemotherapy resistance sensitizer.
The invention provides Biochanin A (Biochanin A) to express and the medicine of relevant disease at preparation suppression ZEB1 Purposes in thing.
Medicine of the present invention includes: ZEB1 micromolecular inhibitor;Suppression breast carcinoma propagation and the medicine of transfer;And Mammary cancer chemotherapy sensitizer.
Biochanin A of the present invention (Biochanin A) is in the expression of preparation suppression ZEB1, and then suppression mammary gland The propagation of cancer, the medicine of transfer and prepare the application in mammary cancer chemotherapy sensitizer, specifically include herein below:
1. the vivoexpression of Biochanin A (Biochanin A) suppression ZEB1 is proved by Western Blot experiment Biochanin A (Biochanin A) can suppress the expression of ZEB1 in breast cancer cell.
2. Biochanin A (Biochanin A) suppression breast carcinoma propagation and the in vitro study of transfer
(1) tested by CCK-8 and confirm that Biochanin A (Biochanin A) is to breast cancer cell MDA-MB-in vitro 231 have grown inhibitory action;
(2) tested by Transwell and confirm that Biochanin A (Biochanin A) is to breast cancer cell in vitro The migration of MDA-MB-231 plays inhibitory action.
3. Biochanin A (Biochanin A) promotes that the in vitro study of mammary cancer chemotherapy enhanced sensitivity is existed by CCK-8 experiment External confirmation Biochanin A (Biochanin A) can strengthen chemotherapeutics epirubicin (Epirubicin) to breast carcinoma The inhibitory action of cell MDA-MB-231 growth.
4. the propagation of the expression of Biochanin A (Biochanin A) suppression ZEB1, and then suppression breast carcinoma, and promote Enter the In vivo study of mammary cancer chemotherapy sensitizer
(1) Female nude mice of 4-6 week old, often group 5 are selected.With 2.0 × 106/ quantity only, inoculates human breast cancer cell MDA-MB-231;
(2) when tumor growth to certain volume, it is respectively adopted the mode of intraperitoneal administration every other day and gavage every other day, gives table Soft than star (5mg/kg) and Biochanin A (100mg/kg);
(3), after being administered two weeks, put to death nude mice, tumor is taken pictures;
(4) the tumor body tag that will take off, 4% paraformaldehyde fixes, and dehydration, paraffin embedding, cuts into slices and carries out pathological staining, The expression of ZEB1 in detection different disposal group.
Advantages of the present invention and good effect:
The Biochanin A (Biochanin A) that the present invention provides can suppress the expression of ZEB1, for ZEB1 inhibitor Preparation provides strategy;Biochanin A (Biochanin A) can suppress propagation and the transfer of breast carcinoma, for breast carcinoma Treatment provides new drug;By by Biochanin A (Biochanin A) and epirubicin use in conjunction, breast carcinoma can be solved Chemotherapy resistance problem.
Accompanying drawing explanation
The molecular structural formula of Fig. 1 Biochanin A (Biochanin A);
Fig. 2 Biochanin A (Biochanin A) suppresses the expression of ZEB1 in breast cancer cell MDA-MB-231;
Fig. 3 Biochanin A (Biochanin A) suppresses it to breed in breast cancer cell MDA-MB-231;
Fig. 4 Biochanin A (Biochanin A) suppresses it to migrate in breast cancer cell MDA-MB-231;
Fig. 5 Biochanin A (Biochanin A) improves the growth of epirubicin in breast cancer cell MDA-MB-231 Rejection ability;
Fig. 6 Biochanin A (Biochanin A) suppression breast carcinoma propagation and the In vivo study of raising chemotherapy sensitizing;
Fig. 7 Biochanin A (Biochanin A) research to ZEB1 expression inhibiting in vivo.
The present invention combines the drawings and specific embodiments and is described in further details.
Detailed description of the invention
Embodiment 1
The expression of Biochanin A (Biochanin A) suppression ZEB1
After Biochanin A (Biochanin A) processes MDA-MB-231 cell 48h, extract albumen, pass through The expression of WesternBlot detection ZEB1;The immunohistochemical experiment of experiment in vivo has also probed into Biochanin A simultaneously (Biochanin A) impact on ZEB1 expression.
As shown in Figure 2 and Figure 7, Fig. 2 Western Blot result shows Biochanin A (Biochanin A) place to result After reason MDA-MB-231 cell, the expression of ZEB1 is substantially suppressed, Fig. 7 Showed by immune group result Biochanin A (Biochanin A) processes after mice, and in its tumor, the expression of ZEB1 is substantially suppressed, and this is that the preparation of ZEB1 inhibitor carries Supply new application.
Embodiment 2
The propagation of Biochanin A (Biochanin A) suppression breast cancer cell
(1) 96 orifice plate, every hole 3000 MDA-MB-231 cells of paving, culture plate is put into incubator.
(2) Biochanin A (Biochanin A) or DMSO process MDA-MB-231 cell 24h, 48h, 72h respectively.
(3) CCK-8 method detection Biochanin A (Biochanin A) inhibitory action to breast cancer cell.
As it is shown on figure 3, Biochanin A (Biochanin A) can substantially suppress the multiplication capacity of breast cancer cell.
Embodiment 3
The transfer of Biochanin A (Biochanin A) suppression breast cancer cell
(1) take MDA-MB-231 cell suspension 200uL and add Transwell cell, use Biochanin A respectively (Biochanin A) or DMSO process.
Under (2) 24 orifice plates, room adds the full culture medium of 500uL, cellar culture 48h.
(3) wipe the cell of upper indoor with cotton swab, violet staining, after three hours, is taken pictures and adds up.
As shown in Figure 4, Biochanin A (Biochanin A) can substantially suppress the transfer ability of breast cancer cell.
Embodiment 4
Biochanin A (Biochanin A) improves the epirubicin rejection ability to breast carcinoma
(1) 96 orifice plate, every hole 3000 MDA-MB-231 cells of paving, culture plate is put into incubator.
(2) DMSO, Biochanin A (Biochanin A), epirubicin or Biochanin A (Biochanin A) and Epirubicin processes MDA-MB-231 cell 48h respectively.
(3) CCK-8 method detection Biochanin A (Biochanin A) and epirubicin are used in combination breast carcinoma thin The inhibitory action of born of the same parents.
As it is shown in figure 5, Biochanin A (Biochanin A) can significantly improve the epirubicin suppression to breast carcinoma Ability.
Embodiment 5
Biochanin A (Biochanin A) suppression breast carcinoma propagation and the In vivo study of raising chemotherapy sensitizing
(1) Female nude mice of 4-6 week old, often group 5 are selected.With 2.0 × 106/ quantity only, inoculates human breast cancer cell MDA-MB-231;
(2) when tumor growth to certain volume, it is respectively adopted the mode of intraperitoneal administration every other day and gavage every other day, gives table Soft than star (5mg/kg) and Biochanin A (100mg/kg);
(3), after being administered two weeks, put to death nude mice, tumor is taken pictures.
As shown in Figure 6, Biochanin A (Biochanin A) can substantially suppress the growth of tumor, and can improve The tumor killing effect of epirubicin.

Claims (4)

1. the Biochanin A (BiochaninA) purposes in the medicine of preparation suppression ZEB1 expression and relevant disease.
Purposes the most according to claim 1, it is characterised in that described medicine is ZEB1 micromolecular inhibitor.
Purposes the most according to claim 1, it is characterised in that described medicine is suppression breast carcinoma propagation, the medicine of transfer Thing.
Purposes the most according to claim 1, it is characterised in that described medicine is mammary cancer chemotherapy sensitizer.
CN201610902969.7A 2016-10-17 2016-10-17 Biochanin A purposes in preparation suppression breast carcinoma propagation, diversion medicaments and mammary cancer chemotherapy sensitizer Pending CN106265631A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110317872A (en) * 2019-07-15 2019-10-11 汕头大学医学院第一附属医院 It is used to prepare the molecular marked compound and kit of detection, prognosis and Diagnosis of Breast cancer product
CN113842387A (en) * 2021-11-19 2021-12-28 大连理工大学盘锦产业技术研究院 Pharmaceutical composition of 10-hydroxycamptothecin and biochanin A and application thereof
CN115335045A (en) * 2020-03-30 2022-11-11 雷根斯堡大学 Mutant bestrophin 1 modulators for the treatment of BEST 1-related retinopathy

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001036004A2 (en) * 1999-11-15 2001-05-25 Parker Hughes Institute Use of egf genistein for treatment egf-receptor expressing cancers
CN1335133A (en) * 2000-07-28 2002-02-13 蛋白质技术国际公司 Composition and method for preventing and curing breast cancer

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001036004A2 (en) * 1999-11-15 2001-05-25 Parker Hughes Institute Use of egf genistein for treatment egf-receptor expressing cancers
CN1335133A (en) * 2000-07-28 2002-02-13 蛋白质技术国际公司 Composition and method for preventing and curing breast cancer

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
《中国医科大学学报》 *
《辽宁中医药大学学报》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110317872A (en) * 2019-07-15 2019-10-11 汕头大学医学院第一附属医院 It is used to prepare the molecular marked compound and kit of detection, prognosis and Diagnosis of Breast cancer product
CN115335045A (en) * 2020-03-30 2022-11-11 雷根斯堡大学 Mutant bestrophin 1 modulators for the treatment of BEST 1-related retinopathy
CN113842387A (en) * 2021-11-19 2021-12-28 大连理工大学盘锦产业技术研究院 Pharmaceutical composition of 10-hydroxycamptothecin and biochanin A and application thereof

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