CN110772511A - 依那普利在制备抗肿瘤药物中的应用 - Google Patents
依那普利在制备抗肿瘤药物中的应用 Download PDFInfo
- Publication number
- CN110772511A CN110772511A CN201911316662.9A CN201911316662A CN110772511A CN 110772511 A CN110772511 A CN 110772511A CN 201911316662 A CN201911316662 A CN 201911316662A CN 110772511 A CN110772511 A CN 110772511A
- Authority
- CN
- China
- Prior art keywords
- enalapril
- treatment
- cancer
- vegf
- ace
- 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
- 108010061435 Enalapril Proteins 0.000 title claims abstract description 38
- 229960000873 enalapril Drugs 0.000 title claims abstract description 38
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 title claims abstract description 38
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 9
- 229940041181 antineoplastic drug Drugs 0.000 title claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 230000012010 growth Effects 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 22
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 22
- 238000011282 treatment Methods 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 16
- 230000033115 angiogenesis Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 11
- 230000004663 cell proliferation Effects 0.000 abstract description 10
- 201000011510 cancer Diseases 0.000 abstract description 9
- 230000037361 pathway Effects 0.000 abstract description 8
- 238000002512 chemotherapy Methods 0.000 abstract description 6
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 5
- 230000004709 cell invasion Effects 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 4
- 102000015427 Angiotensins Human genes 0.000 abstract description 3
- 108010064733 Angiotensins Proteins 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract description 3
- 101150059573 AGTR1 gene Proteins 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 238000011269 treatment regimen Methods 0.000 abstract description 2
- 102100028255 Renin Human genes 0.000 abstract 1
- 108090000783 Renin Proteins 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 25
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 23
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 11
- 239000005541 ACE inhibitor Substances 0.000 description 11
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 11
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 11
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 11
- 101800000733 Angiotensin-2 Proteins 0.000 description 10
- 102400000345 Angiotensin-2 Human genes 0.000 description 10
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 10
- 229950006323 angiotensin ii Drugs 0.000 description 10
- 230000036454 renin-angiotensin system Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000013508 migration Methods 0.000 description 7
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 6
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000012292 cell migration Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 206010014733 Endometrial cancer Diseases 0.000 description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 description 4
- 229940127088 antihypertensive drug Drugs 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 description 3
- 239000002870 angiogenesis inducing agent Substances 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 206010046766 uterine cancer Diseases 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 230000003527 anti-angiogenesis Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000002357 endometrial effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 230000037314 wound repair Effects 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010066671 Enalaprilat Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
- 101000686246 Homo sapiens Ras-related protein R-Ras Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102100024683 Ras-related protein R-Ras Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010047141 Vasodilatation Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229960002680 enalaprilat Drugs 0.000 description 1
- LZFZMUMEGBBDTC-QEJZJMRPSA-N enalaprilat (anhydrous) Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 LZFZMUMEGBBDTC-QEJZJMRPSA-N 0.000 description 1
- 210000005168 endometrial cell Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 230000013152 negative regulation of cell migration Effects 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000009443 proangiogenesis Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000024883 vasodilation Effects 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明提供一种依那普利在抗肿瘤药物中的新应用，依那普利对肾素血管紧张素系统(VEGF介导的血管生成系统的调节者)、参与调节细胞增殖和细胞侵袭的ACE/AngII/AT1R通路发生作用。治疗药物能够作用于参与调节细胞增殖和侵袭的ACE通路。此种治疗方式不仅可以在整个治疗期间使用，还可以在治疗成功后用于预防癌症复发。依那普利作为抗癌药物的使用也有助于改善现有化疗的心血管副作用。
Description
技术领域
本发明涉及抗肿瘤药物，具体涉及依那普利在制备抗肿瘤药物中的应用。
背景技术
血管内皮生长因子(vascular endothelial growth factor，VEGF)，又称血管通透因子(vascular permeability factor，VPF)是一种高度特异性的促血管内皮细胞生长因子，具有促进血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用。通过抑制血管生成控制肿瘤生长一直是癌症生物学探索的方向，抑制血管生成使癌细胞无法生长和扩散。
因为癌细胞增殖需要进行“血管表型”转换并提高大量血管生成因子的产率，包括血管内皮生长因子(VEGF)和刺激VEGF的因子。而血管紧张素系统(RAS)正是这样一种系统，并且与血压调节有关。血管紧张素II(Ang II)是血管紧张素系统的主要效应肽，它既能提高VEGF和VEGF2R的水平又能促进细胞增殖和新陈代谢。血管生成和“血管表型”转换是肿瘤生长和扩散的关键，这种转换与许多血管生成因子的增加有关，包括血管内皮生长因子(VEGF)和刺激VEGF的因子，如肾素血管紧张素系统。
依那普利为血管紧张素转换酶抑制剂(ACEI)。口服后在体内水解成依那普利拉，对血管紧张素转化酶起强烈抑制作用，降低血管紧张素Ⅱ的含量，造成全身血管舒张，血压下降，用于治疗高血压。未有研究将依那普利用于抗肿瘤治疗的药物中，并且现有的抗肿瘤化疗疗法有严重的副作用，可能引起心血管疾病如心肌缺血、梗塞、心力衰竭、高血压、血栓等症状的发生。作为癌症治疗的一部分，尽管这些副作用在可接受的风险范围之内，但在接受其他现有化疗时，会对患者生活质量和正常的治疗进展产生重大影响，从而影响患者的整体预后。这也意味着此现有的抗肿瘤化疗疗法只能在患者需要恢复之前的一段有限的时间内使用。因此，依那普利作为抗癌药物可以控制心血管形成，癌细胞的发育，迁移的使用，并且也有助于改善现有化疗的心血管副作用。
发明内容
针对上述问题，本发明的目的提供依那普利在用于抗肿瘤药物的新应用。
本发明提供一种依那普利在制备抗肿瘤药物中的应用。
本发明提供一种依那普利在抑制血管生长中的应用。
所述肿瘤包括肺癌、肝癌、胃癌、乳腺癌、宫颈癌中的一种或多种。
所述依那普利具有如下结构式
研究表明，依那普利为血管紧张素转换酶抑制剂(ACEI),对血管紧张素转化酶起抑制作用，降低血管紧张素Ⅱ的含量。组织肾素血管紧张素系统(RAS)能够通过血管紧张素II(AngII)1型受体(AT1R)提高血管内皮生长因子(VEGF)的产率。Ang II使低氧诱导因子(HIF-1α)保持稳定，从而导致VEGF的水平升高。Ang II通过自身的AT1R发生作用，促进肿瘤细胞的增殖。现有抗血管生成疗法与本专利提出的疗法的最大不同之处在于，本发明将应用现有的日常使用的抗高血压药物依那普利(Enalapril)来抗血管生成，由于依那普利是一种常用药物，因此人们已充分了解它们的不良反应，并且对患者生活质量的影响微乎其微。此外，这些抗高血压药物还对肾素血管紧张素系统(VEGF介导的血管生成系统的调节者)、参与调节细胞增殖和细胞侵袭的AT1R通路发生作用。因此，不需要仅在治疗期间使用这种治疗方法，它可用于癌症治疗期间、治疗之后，或者在治疗成功后作为延长癌症存活期的手段。这种治疗方式对患者生活质量的影响是最小的。治疗药物能够作用于参与调节细胞增殖和侵袭的ACE/ANG II/AT1R通路。此种治疗方式不仅可以在整个治疗期间使用，还可以在治疗成功后用于预防癌症复发。本发明对肾素血管紧张素系统(RAS)通路在子宫内膜细胞中的表达进行了体外研究，观察子宫内膜上皮癌细胞系(ECC-1)，它可以产生血管紧张素II(Ang II),并与自身的AT1Rs(促血管生成和增殖)相互作用。在子宫内膜上皮癌细胞系(ECC-1)细胞中，连续24小时细胞自生的Ang II血管内皮生长因子(VEGF)信使RNA(mRNA)比ACE拮抗剂(ACEI)的VEGF的表达还要高(P＝0.002未公开)。因此，研究原理证明在子宫内膜癌细胞系中，阻断ACE/Ang II/AT1R通路的药物会抑制具有致癌作用的关键血管生成因子的表达。
本发明的优点在于：
本发明将现有抗血管生成疗法与本专利提出的疗法的最大不同之处在于，本发明将应用现有的日常使用的抗高血压药物依那普利(Enalapril)来抗血管生成是一种常用药物，因此人们已充分了解它们的不良反应，并且对患者生活质量的影响微乎其微。此外，这些抗高血压药物还对肾素血管紧张素系统(VEGF介导的血管生成系统的调节者)、参与调节细胞增殖和细胞侵袭的ACE/AngII/AT1R通路发生作用。因此，不需要仅在治疗期间使用这种治疗方法，它可用于癌症治疗期间、治疗之后，或者在治疗成功后作为延长癌症存活期的手段。这种治疗方式对患者生活质量的影响是最小的。治疗药物能够作用于参与调节细胞增殖和侵袭的ACE通路。此种治疗方式不仅可以在整个治疗期间使用，还可以在治疗成功后用于预防癌症复发。因此，依那普利作为抗癌药物可以控制心血管形成，癌细胞的发育，迁移的使用，并且也有助于改善现有化疗的心血管副作用。
附图说明
图1，血管生成的组织肾素血管紧张素系统通路和下游效应。红色标志代表血管紧张素转化酶抑制剂(ACEIs)的作用地点。
图2，和对照细胞相比血管紧张素II(AngII)促进子宫内膜上皮癌细胞系(ECC-1)中血管内皮生长因子(VEGF)的表达，而ACE抑制剂、依那普利(enalapril)则会抑制血管内皮生长因子(VEGF)的表达。
图3，通过MTT和创伤修复实验(划痕实验)，证明在大多癌细胞系中，和对照细胞相比血管紧张素II(Ang II)可以促进细胞增殖和迁移。而依那普利(enalapril)在大多数被测试的细胞系中抑制细胞增殖和迁移的作用显著(P＜0.05)。
具体实施方式
下面通过具体实施例对本发明作进一步详述，以下实施例只是描述性的，不是限定性的，不能以此限定本发明的保护范围。
图1所示的，此方法的作用方式是通过使用依那普利来抑制负责Ang I向Ang II转化的血管紧张素转换酶(ACE)，因此被称为ACE抑制剂(ACEIs)，因此降低Ang II总量。AngII即Ang II 1型受体的结合负责引发大部分与RAS相关的活动，包括血管生成、细胞增殖和迁移。我们所提出的方法能够抑制肿瘤内部及肿瘤周边区域的血管生成、细胞增殖等活动，以直接和间接地双向抑制肿瘤细胞的增长(减少氧气和营养供给)。
我们对肾素血管紧张素系统(RAS)通路在子宫内膜细胞中的表达进行了体外研究，观察子宫内膜上皮癌细胞系(ECC-1)，它可以产生血管紧张素转化酶(ACE)，血管紧张素II(AngII),并与自身的AT1Rs(促血管生成和增殖)相互作用。
图2所示，使用子宫内膜癌细胞系(ECC-1)测量血管生成活性，血管内皮生长因子(VEGF)是新血管形成(血管生成)的关键因素。我们测量了在不含药物复合物的培养基(对照组Con)、100nM Ang II(Ang II组)、2uM ACEI依那普利(Enalapril组)培养的ECC-1细胞的在48小时内的mRNA表达。我们发现Ang II如预期一样显著促进了VEGF的表达，因为它刺激了AT1R通路(P＜0.038)。而和对照组相比依那普利(Enalapril)显著抑制了ECC-1细胞中VEGF的表达(P＝0.002)，从而抑制血管生成的信号。因此，研究原理证明在子宫内膜癌细胞系中，阻断ACE，以及随后的ANGII/AT1R通路的药物会抑制具有致癌作用的关键血管生成因子的表达。
图3所示，利用子宫内膜癌细胞系ECC-1、HEC-1、Ishikawa和RL95-2测定增殖(细胞生长)和迁移(侵袭和转移的重要因素)活性。这些细胞分别在不含药物复合物的培养基(对照组)，100nM Ang II(Ang II组)和2uM ACEI依那普利(依那普利组)中培养48小时。我们通过MTT试验观察总细胞数来测量增殖情况，并通过创伤修复(划痕试验)来测量迁移。我们发现，与对照组相比，Ang II显著促进了四个细胞系的细胞增殖，而依那普利(Enalapril)显著抑制了HEC-1、Ishikawa和RL95-2细胞系的增殖，并能够在一定程度上抑制ECC-1细胞的增殖。与对照组相比，Ang II显著促进了ECC-1和HEC-1细胞系的细胞迁移，而对Ishikawa和RL95-2细胞迁移没有显著影响。与对照组相比，依那普利(Enalapril)仅抑制了Ishikawa和RL95-2细胞迁移。
最后应说明的是：以上各实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述各实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分或者全部技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (4)
1.依那普利在制备抗肿瘤药物中的应用。
2.依那普利在抑制血管生长中的应用。
3.根据权利要求1所述的应用，其特征在于，所述肿瘤包括肺癌、肝癌、胃癌、乳腺癌、宫颈癌中的一种或多种。
4.根据权利要求1-3任意一项所述的应用，其特征在于，所述依那普利具有如下结构式
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911316662.9A CN110772511A (zh) | 2019-12-19 | 2019-12-19 | 依那普利在制备抗肿瘤药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911316662.9A CN110772511A (zh) | 2019-12-19 | 2019-12-19 | 依那普利在制备抗肿瘤药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110772511A true CN110772511A (zh) | 2020-02-11 |
Family
ID=69394690
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911316662.9A Pending CN110772511A (zh) | 2019-12-19 | 2019-12-19 | 依那普利在制备抗肿瘤药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110772511A (zh) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030203834A1 (en) * | 2002-02-27 | 2003-10-30 | Tallant E. Ann | Angiotensin-(1-7) and angiotensin-(1-7) agonists for inhibition of cancer cell growth |
-
2019
- 2019-12-19 CN CN201911316662.9A patent/CN110772511A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030203834A1 (en) * | 2002-02-27 | 2003-10-30 | Tallant E. Ann | Angiotensin-(1-7) and angiotensin-(1-7) agonists for inhibition of cancer cell growth |
Non-Patent Citations (4)
| Title |
|---|
| M. PAWLIKOWSKI等: "The involvement of the renin-angiotensin system in the", 《CELL. MOL. LIFE SCI.》 * |
| 张铭娜等: ""血管紧张素Ⅱ及其Ⅰ型受体与妇科肿瘤"", 《国际妇产科学杂志》 * |
| 李大魁: "《中华医学百科全书 药学 临床药学》", 31 December 2018 * |
| 胡维维等: "血管紧张素Ⅱ1 型受体和血管紧张素转化酶在子宫内", 《临床与实验病理学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Miner et al. | A look between the cardiomyocytes: the extracellular matrix in heart failure | |
| JP5650639B2 (ja) | 腫瘍疾患の治療 | |
| Unger et al. | Therapeutic perspectives in hypertension: novel means for renin–angiotensin–aldosterone system modulation and emerging device-based approaches | |
| Kubicek et al. | Phase I trial using the proteasome inhibitor bortezomib and concurrent chemoradiotherapy for head-and-neck malignancies | |
| Wang et al. | Dual PLK1 and STAT3 inhibition promotes glioblastoma cells apoptosis through MYC | |
| Emmanouilides et al. | Anti-VEGF antibody bevacizumab (Avastin) with 5FU/LV as third line treatment for colorectal cancer | |
| Hockey et al. | Dexamethasone for intracranial neurosurgery and anaesthesia | |
| EP3269393A1 (en) | Hsp90 inhibition peptide conjugate and application thereof in treating tumor | |
| Komaki et al. | Improvement strategies for molecular targeting: cyclooxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer | |
| CA2582048A1 (en) | Use of angiotensin-(1-7) for preventing and/or reducing the formation of neointima | |
| Sadek et al. | Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME) induced hypertension in rats | |
| CN110772511A (zh) | 依那普利在制备抗肿瘤药物中的应用 | |
| Azzam et al. | Taming resistant hypertension: The promise of novel pharmacologic approaches and renal denervation | |
| Tang et al. | Aldosterone receptor antagonists in the medical management of chronic heart failure | |
| CN106163518B (zh) | 包含血管紧张素-Ⅱ受体阻断剂和HMG-CoA还原酶抑制剂的药物组合制剂 | |
| Abrahamsson et al. | Risks and benefits of hormonal manipulation as monotherapy or adjuvant treatment in localised prostate cancer | |
| ES2870909T3 (es) | Usos de un compuesto en la preparación de fármacos para el tratamiento del glioma cerebral | |
| CN110812356A (zh) | 氯沙坦在制备抗肿瘤药物中的应用 | |
| Fiebeler et al. | Participation of the mineralocorticoid receptor in cardiac and vascular remodeling | |
| Hoffman et al. | EFFECT OF COMBINATION THERAPY OF DESMOPRESSIN AND DOCETAXEL ON PROSTATE CANCER CELL DU145 PROLIFERATION, MIGRATION AND GROWTH: MP83-17 | |
| CN115429882B (zh) | 伤害性感觉神经细胞调控药物的用途 | |
| Kitlinska et al. | Role of neuropeptide Y and dipeptidyl peptidase IV in regulation of Ewing’s sarcoma growth | |
| Fuchs et al. | Pharmacotherapy of chronic heart failure: current status and future aspects | |
| Pimenta et al. | What is new in the management of resistant hypertension? | |
| KR101933805B1 (ko) | 옥셀라딘시트레이트를 유효성분으로 포함하는 뇌암 예방 또는 치료용 약학적 조성물 |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200211 |