CN115463122A - 一种增强盐霉素抗癌活性的方法及应用 - Google Patents
一种增强盐霉素抗癌活性的方法及应用 Download PDFInfo
- Publication number
- CN115463122A CN115463122A CN202210980302.4A CN202210980302A CN115463122A CN 115463122 A CN115463122 A CN 115463122A CN 202210980302 A CN202210980302 A CN 202210980302A CN 115463122 A CN115463122 A CN 115463122A
- Authority
- CN
- China
- Prior art keywords
- salinomycin
- bibr1532
- telomerase
- anticancer activity
- telomere
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- KQXDHUJYNAXLNZ-XQSDOZFQSA-N Salinomycin Chemical compound O1[C@@H]([C@@H](CC)C(O)=O)CC[C@H](C)[C@@H]1[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@H](CC)[C@@H]1[C@@H](C)C[C@@H](C)[C@@]2(C=C[C@@H](O)[C@@]3(O[C@@](C)(CC3)[C@@H]3O[C@@H](C)[C@@](O)(CC)CC3)O2)O1 KQXDHUJYNAXLNZ-XQSDOZFQSA-N 0.000 title claims abstract description 68
- 239000004189 Salinomycin Substances 0.000 title claims abstract description 68
- 229960001548 salinomycin Drugs 0.000 title claims abstract description 68
- 235000019378 salinomycin Nutrition 0.000 title claims abstract description 68
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 17
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims abstract description 11
- PGFQXGLPJUCTOI-WYMLVPIESA-N BIBR-1532 Chemical compound C=1C=C2C=CC=CC2=CC=1C(/C)=C/C(=O)NC1=CC=CC=C1C(O)=O PGFQXGLPJUCTOI-WYMLVPIESA-N 0.000 claims abstract description 46
- 230000000694 effects Effects 0.000 claims abstract description 35
- 108010017842 Telomerase Proteins 0.000 claims abstract description 15
- 108091035539 telomere Proteins 0.000 claims abstract description 7
- 102000055501 telomere Human genes 0.000 claims abstract description 7
- 230000003197 catalytic effect Effects 0.000 claims abstract description 5
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 108010057210 telomerase RNA Proteins 0.000 claims abstract description 5
- 229940123582 Telomerase inhibitor Drugs 0.000 claims abstract description 4
- 239000003277 telomerase inhibitor Substances 0.000 claims abstract description 4
- 102100034343 Integrase Human genes 0.000 claims abstract description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims abstract description 3
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 3
- 230000003252 repetitive effect Effects 0.000 claims abstract description 3
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 230000007246 mechanism Effects 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 23
- 206010028980 Neoplasm Diseases 0.000 abstract description 13
- 201000011510 cancer Diseases 0.000 abstract description 4
- 230000006378 damage Effects 0.000 abstract description 2
- 210000003411 telomere Anatomy 0.000 abstract 4
- 108020004414 DNA Proteins 0.000 abstract 1
- 230000006820 DNA synthesis Effects 0.000 abstract 1
- 208000027418 Wounds and injury Diseases 0.000 abstract 1
- 208000014674 injury Diseases 0.000 abstract 1
- 238000012423 maintenance Methods 0.000 abstract 1
- 238000004904 shortening Methods 0.000 abstract 1
- 238000013518 transcription Methods 0.000 abstract 1
- 230000035897 transcription Effects 0.000 abstract 1
- 230000003833 cell viability Effects 0.000 description 12
- 239000004005 microsphere Substances 0.000 description 7
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 238000012258 culturing Methods 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 108010087230 Sincalide Proteins 0.000 description 3
- 238000010609 cell counting kit-8 assay Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000053067 Pyruvate Dehydrogenase Acetyl-Transferring Kinase Human genes 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 101710159466 [Pyruvate dehydrogenase (acetyl-transferring)] kinase, mitochondrial Proteins 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- -1 and the like Chemical compound 0.000 description 1
- 229940124536 anticoccidial agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000003224 coccidiostatic agent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000002460 polyether antibiotic agent Substances 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/35—Heterocyclic 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
- A61K31/351—Heterocyclic 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 not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
- Y02A40/70—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in livestock or poultry
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种增强盐霉素抗癌活性的方法及应用。端粒酶作为一种逆转录酶,能以TERC为模板,利用TERT的催化功能把TTAGGG重复序列加在端粒末端,通过端粒DNA合成功能防止端粒缩短,使癌细胞永生化,除了传统的端粒延伸功能,TERT在癌细胞中还与基因转录、DNA损伤修复、干性维持及ROS调节等密切相关。本发明使用端粒酶抑制剂BIBR1532抑制端粒酶活性,从而提高盐霉素的抗癌活性,靶向端粒酶是增强盐霉素抗癌活性且对正常细胞影响小的有效策略。
Description
技术领域
本发明涉及医药化学技术领域,特别是涉及一种增强盐霉素抗癌活性的方法及应用。
背景技术
盐霉素是70年代初从白色链霉菌培养基中提取的一种单羧基聚醚类抗生素。在很长一段时间内,盐霉素只作为一种抗球虫药用于家畜疾病的治疗。直到2009年,温伯格团队发现盐霉素具有抗癌功能。随后的研究表明,盐霉素能够抑制多种癌细胞活性。而且,与传统化疗药物紫杉醇、阿霉素、顺铂、替莫唑胺等不同,盐霉素不仅能杀伤癌细胞,还能够清除肿瘤干细胞样细胞和多药耐药细胞。鉴于这些优势,盐霉素受到了科学家的高度重视,被认为具有开发为高效抗癌药物的潜力。但是,高浓度盐霉素可以导致哺乳动物产生严重的全身不良反应,从而阻碍了其在人类疾病治疗中的应用。虽然很多提高盐霉素抗癌活性从而降低盐霉素使用量的方法被发现,例如将盐霉素与靶向组蛋白去乙酰化酶、丙酮酸脱氢酶激酶或自噬过程的化合物联合使用,但是,这些方法本身会引起正常细胞损伤。因此,寻找更有效的增强盐霉素抗癌活性且对正常细胞影响小的方法是亟待解决的问题。
发明内容
本发明的目的就在于为了解决上述问题而提供一种增强盐霉素抗癌活性的方法及应用。
本发明通过以下技术方案来实现上述目的:
一种增强盐霉素抗癌活性的方法及应用,使用端粒酶抑制剂抑制端粒酶活性,提高盐霉素的抗癌活性;
其机理是:端粒酶是一种逆转录酶,由RNA模板TERC及蛋白催化亚基TERT组成,端粒酶能以TERC为模板,利用TERT的催化功能把TTAGGG重复序列加在端粒末端,在癌细胞中,端粒酶能够通过端粒DNA合成功能防止端粒缩短,使癌细胞永生化,TERT在癌细胞中还与基因转录、DNA损伤修复、干性维持及ROS调节密切相关,靶向端粒酶是增强盐霉素抗癌活性且对正常细胞影响小的有效方法。
其中,所述的端粒酶抑制为BIBR1532。
与现有技术相比,本发明的有益效果如下:
使用端粒酶抑制剂BIBR1532抑制端粒酶活性,从而提高盐霉素的抗癌活性,靶向端粒酶是增强盐霉素抗癌活性且对正常细胞影响小的有效策略。
附图说明
图1是BIBR1532与盐霉素的结构式;
图2是BIBR1532与盐霉素同时处理对MCF-7细胞活力的影响;
图3是BIBR1532与盐霉素同时处理对MDA-MB-231细胞活力的影响;
图4是BIBR1532与盐霉素同时处理对微球体形态的影响;
图5是BIBR1532与盐霉素同时处理对微球体数量的影响;
图6是BIBR1532与盐霉素同时处理对ROS产生的影响;
图7是BIBR1532、盐霉素及ROS清除剂NAC同时处理对MCF-7细胞活力的影响;
图8是BIBR1532与盐霉素同时处理对肿瘤生长的影响;
图9是BIBR1532与盐霉素同时处理对肿瘤组织形态的影响。
具体实施方式
下面结合附图对本发明作进一步说明:
实施例1
BIBR1532与盐霉素同时处理对MCF-7细胞活力的影响
将MCF-7细胞以1×104个/孔的密度接种到96孔培养板中,接种之后将培养板置于37℃、5%CO2、潮湿的培养箱中培养24h。加入BIBR1532及盐霉素,使BIBR1532的终浓度为15μM,盐霉素的浓度分别为1、2、4、8、16μM,并将培养板放回培养箱中继续培养72h。加入CCK-8溶液(10μL/孔),培养箱中培养2h。最后将培养板置于酶标仪中,450nm测量吸光度。使用吸光度值计算细胞相对活力。图2是BIBR1532与盐霉素同时处理对MCF-7细胞活力的影响。图2显示BIBR1532能够增强不同浓度盐霉素对MCF-7细胞活力的抑制作用,说明BIBR1532能够增强盐霉素对乳腺癌的抑制作用。
实施例2
BIBR1532与盐霉素同时处理对MDA-MB-231细胞活力的影响
将MDA-MB-231细胞以1×104个/孔的密度接种到96孔培养板中,接种之后将培养板置于37℃、5%CO2、潮湿的培养箱中培养24h。加入BIBR1532及盐霉素,使BIBR1532的终浓度为15μM,盐霉素的浓度分别为1、2、4、8、16μM,并将培养板放回培养箱中继续培养72h。加入CCK-8溶液(10μL/孔),培养箱中培养2h。最后将培养板置于酶标仪中,450nm测量吸光度。使用吸光度值计算细胞相对活力。图3是BIBR1532与盐霉素同时处理对MDA-MB-231细胞活力的影响。图3显示BIBR1532能够增强不同浓度盐霉素对MDA-MB-231细胞活力的抑制作用,说明BIBR1532能够增强盐霉素对乳腺癌的抑制作用。
实施例3
BIBR1532与盐霉素同时处理对微球体形成的影响
将MCF-7细胞以5000个/孔的密度接种到DMEM/F12培养基中,在其中添加20ng/mL碱性成纤维生长因子bFGF、20ng/mL人重组上皮生长因子EGF、4μg/mL肝素、1%链霉素和青霉素,并在6孔超低粘附培养板中培养。同时加入BIBR1532与盐霉素,使BIBR1532的浓度为15μM,盐霉素浓度为4μM。7天后,在显微镜下观察微球体形态和数量,并拍照。图4是BIBR1532与盐霉素同时处理对微球体形态的影响。图5是BIBR1532与盐霉素同时处理对微球体数量的影响。从图4和图5可以看出,BIBR1532能够增强盐霉素对微球体形成的抑制作用,说明BIBR1532能够增强盐霉素对肿瘤干细胞样细胞的抑制作用。
实施例4
BIBR1532与盐霉素同时处理对ROS产生的影响
将MCF-7细胞以1×106个/孔的密度接种到6孔培养板中,接种之后将培养板置于37℃、5%CO2、潮湿的培养箱中培养24h。加入BIBR1532及盐霉素,使BIBR1532的终浓度为15μM,盐霉素的浓度为8μM,并将培养板放回培养箱中继续培养72h。加入DCFH-DA(10μM)孵育30min,用流式细胞技术检测细胞内ROS含量。图6是BIBR1532与盐霉素同时处理MCF-7细胞后,细胞中ROS的水平。图6显示,BIBR1532能够在乳腺癌细胞中增强盐霉素诱导的ROS产生。
实施例5
BIBR1532、盐霉素及ROS清除剂(N-乙酰-L-半胱氨酸,NAC)同时处理对MCF-7细胞活力的影响
将MCF-7细胞以1×104个/孔的密度接种到96孔培养板中,接种之后将培养板置于37℃、5%CO2、潮湿的培养箱中培养24h。加入BIBR1532、盐霉素及NAC,使BIBR1532的终浓度为15μM、盐霉素浓度为8μM、NAC浓度为10mM。48h或72h后,加入CCK-8溶液(10μL/孔),孵育2h。最后将培养板置于酶标仪中,450nm测量吸光度。使用吸光度值计算细胞相对活力。图7是BIBR1532、盐霉素及NAC同时处理对MCF-7细胞活力的影响。图7说明清除ROS能够部分逆转BIBR1532与盐霉素诱导的MCF-7细胞活力抑制。
实施例6
BIBR1532与盐霉素同时处理对肿瘤生长的影响
将5×106个MCF-7细胞注射到BALB/c免疫缺陷鼠皮下。待肿瘤体积达到150mm3时,每3天注射一次BIBR1532(1.5mg/kg)与盐霉素(2mg/kg),并且每3天用游标卡尺测量、记录一次肿瘤体积。肿瘤体积计算公式为:长×宽2/2(mm3)。36天后,取出肿瘤组织,进行石蜡包埋、切片、HE染色,并在光学显微镜下观察肿瘤组织。图8是BRBI1532与盐霉素同时处理对肿瘤生长的影响;图9是BIBR1532与盐霉素同时处理对肿瘤组织的影响。从图8与图9可以看出,BIBR1532能够增强盐霉素对肿瘤生长的抑制作用,并能增强盐霉素对肿瘤组织的破坏作用。
Claims (2)
1.一种增强盐霉素抗癌活性的方法及应用,其特征在于:使用端粒酶抑制剂抑制端粒酶活性,提高盐霉素的抗癌活性;
其机理是:端粒酶是一种逆转录酶,由RNA模板TERC及蛋白催化亚基TERT组成,端粒酶能以TERC为模板,利用TERT的催化功能把TTAGGG重复序列加在端粒末端,在癌细胞中,端粒酶能够通过端粒DNA合成功能防止端粒缩短,使癌细胞永生化,TERT在癌细胞中还与基因转录、DNA损伤修复、干性维持及ROS调节密切相关,靶向端粒酶是增强盐霉素抗癌活性且对正常细胞影响小的有效方法。
2.根据权利要求1所述的一种增强盐霉素抗癌活性的方法及应用,其特征在于:所述的端粒酶抑制为BIBR1532。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210980302.4A CN115463122A (zh) | 2022-08-16 | 2022-08-16 | 一种增强盐霉素抗癌活性的方法及应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210980302.4A CN115463122A (zh) | 2022-08-16 | 2022-08-16 | 一种增强盐霉素抗癌活性的方法及应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115463122A true CN115463122A (zh) | 2022-12-13 |
Family
ID=84366713
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210980302.4A Pending CN115463122A (zh) | 2022-08-16 | 2022-08-16 | 一种增强盐霉素抗癌活性的方法及应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115463122A (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101353646A (zh) * | 2008-03-13 | 2009-01-28 | 首都医科大学北京神经科学研究所 | 端粒酶永生化人胚胎前脑神经前体细胞系及其建立方法 |
CN102816239A (zh) * | 2011-06-09 | 2012-12-12 | 深圳雅臣生物科技有限公司 | 抗端粒酶逆转录酶和人表皮生长因子受体特异性复合IgY及其制备方法 |
-
2022
- 2022-08-16 CN CN202210980302.4A patent/CN115463122A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101353646A (zh) * | 2008-03-13 | 2009-01-28 | 首都医科大学北京神经科学研究所 | 端粒酶永生化人胚胎前脑神经前体细胞系及其建立方法 |
CN102816239A (zh) * | 2011-06-09 | 2012-12-12 | 深圳雅臣生物科技有限公司 | 抗端粒酶逆转录酶和人表皮生长因子受体特异性复合IgY及其制备方法 |
Non-Patent Citations (6)
Title |
---|
AN H, KIM J Y, OH E, ET AL.: "Salinomycin promotes anoikis and decreases the CD44+/CD24-stem-like population via inhibition of STAT3 activation in MDA-MB-231 cells", 《PLOS ONE 》, vol. 10, 3 November 2015 (2015-11-03), pages 1 - 6 * |
DOĞAN F, ÖZATEŞ N P, BAĞCA B G, ET AL.: "Investigation of the effect of telomerase inhibitor BIBR1532 on breast cancer and breast cancer stem cells", 《JOURNAL OF CELLULAR BIOCHEMISTRY 》, vol. 120, 28 October 2018 (2018-10-28), XP071663647, DOI: 10.1002/jcb.27089 * |
WANG H, ZHANG H, ZHU Y, ET AL.: "Anticancer mechanisms of salinomycin in breast cancer and its clinical applications", 《FRONTIERS IN ONCOLOGY 》, vol. 11, 26 July 2021 (2021-07-26), pages 1 - 2 * |
张静;刘照旭;杨金玲;陈新霞;娄凤兰;徐大为;: "BIBR1532对p53和pRb功能缺陷的肿瘤细胞生长抑制作用的研究", 山东大学学报(医学版), no. 11, 28 November 2006 (2006-11-28) * |
王凡;郭传勇;: "盐霉素――一种新型的抗肿瘤药物", 同济大学学报(医学版), no. 03, 15 June 2013 (2013-06-15) * |
钱东;丁小凤;程菁菁;袁智勇;: "靶向端粒 端粒酶的抗肿瘤治疗研究进展", 中国肿瘤临床, no. 15, 15 August 2016 (2016-08-15) * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN117298104B (zh) | Elovl6-in-2在制备mycn扩增型神经母细胞瘤药物中的应用 | |
CN101972247A (zh) | 15-苄亚基-14-脱氧-11,12-脱氢穿心莲内酯衍生物的药物用途 | |
CN107669686B (zh) | 毛蕊异黄酮衍生物在制备治疗er阴性乳腺癌药物中的应用 | |
CN115463122A (zh) | 一种增强盐霉素抗癌活性的方法及应用 | |
JP5696191B2 (ja) | 抗癌幹細胞剤 | |
JP6264685B2 (ja) | マルチキナーゼ阻害剤、抗癌剤、抗転移剤、薬剤耐性抑制剤、疼痛抑制剤及び止痒薬 | |
CN115364109B (zh) | 一种用于肺癌治疗的药物制剂 | |
CN108295085B (zh) | 原薯蓣皂苷在制备抗耐药性骨肉瘤药物中的应用 | |
CN115990264A (zh) | 一种ptk7靶向核酸适体偶联药物 | |
CN107698639B (zh) | 一类吉西他滨磷酸酯的n-甲酸酯乏氧活化前药及其应用 | |
CN107496428B (zh) | 毛蕊异黄酮衍生物在制备促进内皮细胞增殖药物中的应用 | |
CN113133999B (zh) | 蛇床子素及其衍生物在抑制醛酮还原酶中的应用 | |
KR100671762B1 (ko) | 암치료와 암예방을 위한 한약조성물 | |
CN110522759B (zh) | miR-517b-3p抑制剂在治疗紫杉醇耐药乳腺癌中的应用 | |
CN112043722B (zh) | Prpf6在前列腺癌及去势抵抗前列腺癌治疗中的应用 | |
CN108992463B (zh) | 一种治疗肺癌的组合物及药物制剂 | |
CN111905102A (zh) | Ezh2抑制剂在治疗胶质瘤中的应用 | |
CN113388615A (zh) | 一种预防和/或治疗急性胰腺炎的miRNA及其制药应用 | |
CN112336716A (zh) | 维生素c和双硫仑在制备抗肿瘤联合用药物中的用途 | |
CN102643811B (zh) | 人miR-1229的反义寡聚核苷酸及其应用 | |
CN1706376A (zh) | 藤黄酸在制备抗肿瘤转移药中的应用 | |
CN110151748A (zh) | 一种用于治疗前列腺癌的药物组合物 | |
CN117731654B (zh) | Jjh201601在初发性脑胶质瘤和复发性脑胶质瘤治疗中的新用途 | |
CN102643814B (zh) | 人miR-431的反义寡聚核苷酸及其应用 | |
CN109692173B (zh) | 一种化合物在制备用于治疗和/或预防肺癌的药物中的用途及其组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |