• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

普萘洛尔通过抑制恶性黑色素瘤的增殖并诱导G0/G1/S期阻滞，增强了舒尼替尼的抗肿瘤作用。

Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma.

作者信息

Kuang Xinwei, Qi Min, Peng Cong, Zhou Chengfang, Su Juan, Zeng Weiqi, Liu Hong, Zhang Jianglin, Chen Mingliang, Shen Minxue, Xie Xiaoyun, Li Fangfang, Zhao Shuang, Li Qingling, Luo Zhongling, Chen Junchen, Tao Juan, He Yijing, Chen Xiang

机构信息

Department of Dermatology, XiangYa Hospital, Central South University, Changsha, China.

Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, China.

出版信息

Oncotarget. 2017 Nov 25;9(1):802-811. doi: 10.18632/oncotarget.22696. eCollection 2018 Jan 2.

DOI:10.18632/oncotarget.22696
PMID:29416656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5787512/
Abstract

Both sunitinib, a multi-target tyrosine kinase inhibitor (TKI) and propranolol, a non-selective β-blocker, have proven therapeutic effects on malignant melanoma (MM). This study reports a synergistic effect of propranolol and sunitinib upon A375, P8 MM cell lines and mice xenografts. Cell viability assays detected a significant decrease of sunitinib IC50 in combination with propranolol, which was confirmed by a colony formation assay. Western blot showed that propranolol and sunitinib combination significantly down-regulated phospho-Rb, phospho-ERK, Cyclin D1, and Cyclin E, but had no effect on Bax, Bcl-2, or cleaved PARP expression. The average tumor size of propranolol and low-dose sunitinib (Sun L) combination treated mice was reduced and similar to high-dose sunitinib treated A375 xenografts. The Ki67 index was significantly reduced in propranolol and Sun L combination treated group compared with single Sun L treated group. This synergistic effect between propranolol and sunitinib to inhibit MM proliferation was through suppressing ERK/Cyclin D1/Rb/Cyclin E pathways and inducing G0/G1/S phase arrest, rather than by inducing tumor cell apoptosis.

摘要

多靶点酪氨酸激酶抑制剂（TKI）舒尼替尼和非选择性β受体阻滞剂普萘洛尔对恶性黑色素瘤（MM）均有已证实的治疗效果。本研究报告了普萘洛尔和舒尼替尼对A375、P8 MM细胞系及小鼠异种移植瘤的协同作用。细胞活力测定检测到舒尼替尼与普萘洛尔联合使用时IC50显著降低，集落形成试验证实了这一点。蛋白质免疫印迹显示，普萘洛尔与舒尼替尼联合使用显著下调磷酸化Rb、磷酸化ERK、细胞周期蛋白D1和细胞周期蛋白E，但对Bax、Bcl-2或裂解的PARP表达无影响。普萘洛尔与低剂量舒尼替尼（Sun L）联合治疗的小鼠平均肿瘤大小减小，与高剂量舒尼替尼治疗的A375异种移植瘤相似。与单剂量Sun L治疗组相比，普萘洛尔与Sun L联合治疗组的Ki67指数显著降低。普萘洛尔与舒尼替尼之间抑制MM增殖的这种协同作用是通过抑制ERK/细胞周期蛋白D1/Rb/细胞周期蛋白E通路并诱导G0/G1/S期阻滞，而非通过诱导肿瘤细胞凋亡实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/bad9c2feeb94/oncotarget-09-802-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/4711c30416f7/oncotarget-09-802-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/543cabb3a08e/oncotarget-09-802-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/467be17afcbb/oncotarget-09-802-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/1392799e74fe/oncotarget-09-802-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/95117560c2f0/oncotarget-09-802-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/c92881effc2b/oncotarget-09-802-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/bad9c2feeb94/oncotarget-09-802-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/4711c30416f7/oncotarget-09-802-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/543cabb3a08e/oncotarget-09-802-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/467be17afcbb/oncotarget-09-802-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/1392799e74fe/oncotarget-09-802-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/95117560c2f0/oncotarget-09-802-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/c92881effc2b/oncotarget-09-802-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a3/5787512/bad9c2feeb94/oncotarget-09-802-g007.jpg

相似文献

1
Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma.普萘洛尔通过抑制恶性黑色素瘤的增殖并诱导G0/G1/S期阻滞，增强了舒尼替尼的抗肿瘤作用。
Oncotarget. 2017 Nov 25;9(1):802-811. doi: 10.18632/oncotarget.22696. eCollection 2018 Jan 2.
2
Propranolol induced G0/G1/S phase arrest and apoptosis in melanoma cells via AKT/MAPK pathway.普萘洛尔通过AKT/MAPK途径诱导黑色素瘤细胞发生G0/G1/S期阻滞和凋亡。
Oncotarget. 2016 Oct 18;7(42):68314-68327. doi: 10.18632/oncotarget.11599.
3
Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer.酪氨酸激酶受体抑制剂靶向联合化疗治疗转移性膀胱癌。
Kaohsiung J Med Sci. 2012 Apr;28(4):194-203. doi: 10.1016/j.kjms.2011.06.020. Epub 2011 Sep 25.
4
Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells.蟾毒灵通过抑制细胞周期蛋白D、细胞周期蛋白E、细胞周期蛋白依赖性激酶2（CDK2）和细胞周期蛋白依赖性激酶4（CDK4）的水平诱导T24人膀胱癌细胞发生G0/G1期阻滞，并通过线粒体信号通路触发细胞凋亡。
Mutat Res. 2012 Apr 1;732(1-2):26-33. doi: 10.1016/j.mrfmmm.2011.09.010. Epub 2012 Jan 20.
5
Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway.雌马酚通过调节Akt信号通路抑制人胃癌细胞的增殖。
World J Gastroenterol. 2015 Sep 28;21(36):10385-99. doi: 10.3748/wjg.v21.i36.10385.
6
Tehranolide inhibits proliferation of MCF-7 human breast cancer cells by inducing G0/G1 arrest and apoptosis.特赫醇内酯通过诱导 G0/G1 期阻滞和细胞凋亡抑制 MCF-7 人乳腺癌细胞的增殖。
Free Radic Biol Med. 2012 May 1;52(9):1987-99. doi: 10.1016/j.freeradbiomed.2012.01.026. Epub 2012 Feb 4.
7
[Growth inhibition of combined pathway inhibitors on KRAS mutated non-small cell lung cancer cell line].联合通路抑制剂对KRAS突变型非小细胞肺癌细胞系的生长抑制作用
Zhonghua Bing Li Xue Za Zhi. 2013 May;42(5):330-5. doi: 10.3760/cma.j.issn.0529-5807.2013.05.009.
8
Manganese chloride-induced G0/G1 and S phase arrest in A549 cells.氯化锰诱导A549细胞发生G0/G1期和S期阻滞。
Toxicology. 2008 Aug 19;250(1):39-46. doi: 10.1016/j.tox.2008.05.016. Epub 2008 Jun 3.
9
Sodium ascorbate inhibits growth via the induction of cell cycle arrest and apoptosis in human malignant melanoma A375.S2 cells.抗坏血酸钠通过诱导人恶性黑色素瘤A375.S2细胞的细胞周期停滞和凋亡来抑制其生长。
Melanoma Res. 2006 Dec;16(6):509-19. doi: 10.1097/01.cmr.0000232297.99160.9e.
10
Dimethylfumarate inhibits melanoma cell proliferation via p21 and p53 induction and bcl-2 and cyclin B1 downregulation.富马酸二甲酯通过诱导p21和p53以及下调bcl-2和细胞周期蛋白B1来抑制黑色素瘤细胞增殖。
Tumour Biol. 2016 Oct;37(10):13627-13635. doi: 10.1007/s13277-016-5285-6. Epub 2016 Jul 29.

引用本文的文献

1
Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.心力衰竭药物治疗与癌症：相关途径和临床前/临床证据。
Eur Heart J. 2024 Apr 7;45(14):1224-1240. doi: 10.1093/eurheartj/ehae105.
2
Trial watch: beta-blockers in cancer therapy.研究观察：β受体阻滞剂在癌症治疗中的应用。
Oncoimmunology. 2023 Nov 27;12(1):2284486. doi: 10.1080/2162402X.2023.2284486. eCollection 2023.
3
Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.溴结构域和末端结构域（BET）蛋白：生物学功能、疾病和靶向治疗。

本文引用的文献

1
Long-Term Response to Sunitinib Treatment in Metastatic Renal Cell Carcinoma: A Pooled Analysis of Clinical Trials.舒尼替尼治疗转移性肾细胞癌的长期反应：临床试验的汇总分析
Clin Genitourin Cancer. 2017 Jun 20. doi: 10.1016/j.clgc.2017.06.005.
2
Sunitinib is effective and tolerable in Chinese patients with advanced pancreatic neuroendocrine tumors: a multicenter retrospective study in China.
Cancer Chemother Pharmacol. 2017 Sep;80(3):507-516. doi: 10.1007/s00280-017-3367-9. Epub 2017 Jul 13.
3
Visceral metastatic angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol.口服环磷酰胺联合普萘洛尔有效治疗内脏转移性血管肉瘤。
Signal Transduct Target Ther. 2023 Nov 6;8(1):420. doi: 10.1038/s41392-023-01647-6.
4
Unlocking therapeutic potential: integration of drug repurposing and immunotherapy for various disease targeting.释放治疗潜力：药物重新利用与免疫疗法针对多种疾病靶点的整合。
Am J Transl Res. 2023 Aug 15;15(8):4984-5006. eCollection 2023.
5
and study on the effect of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of melanoma cells.以及关于卡维地洛和索拉非尼单独及联合使用对黑色素瘤细胞生长和炎症反应影响的研究。
Saudi Pharm J. 2023 Jul;31(7):1306-1316. doi: 10.1016/j.jsps.2023.05.020. Epub 2023 May 26.
6
BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.BET 抑制剂通过抑制 GDF15 与舒尼替尼在黑色素瘤中协同作用。
Exp Mol Med. 2023 Feb;55(2):364-376. doi: 10.1038/s12276-023-00936-y. Epub 2023 Feb 1.
7
Propranolol: A "Pick and Roll" Team Player in Benign Tumors and Cancer Therapies.普萘洛尔：良性肿瘤与癌症治疗中的“挡拆配合”团队成员
J Clin Med. 2022 Aug 4;11(15):4539. doi: 10.3390/jcm11154539.
8
The Effect of Beta Adrenoreceptor Blockers on Viability and Cell Colony Formation of Non-Small Cell Lung Cancer Cell Lines A549 and H1299.β肾上腺素能受体阻滞剂对非小细胞肺癌细胞系 A549 和 H1299 活力和细胞集落形成的影响。
Molecules. 2022 Mar 17;27(6):1938. doi: 10.3390/molecules27061938.
9
Sunitinib malate inhibits hemangioma cell growth and migration by suppressing focal adhesion kinase signaling.马来酸舒尼替尼通过抑制黏着斑激酶信号通路抑制血管细胞瘤细胞的生长和迁移。
J Appl Biomed. 2020 Dec;18(4):143-151. doi: 10.32725/jab.2020.019. Epub 2020 Dec 7.
10
Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux.普萘洛尔通过改变溶酶体药物隔离和药物外排使血管肉瘤细胞对阿霉素敏感。
Front Oncol. 2021 Feb 1;10:614288. doi: 10.3389/fonc.2020.614288. eCollection 2020.
JAAD Case Rep. 2016 Dec 7;2(6):497-499. doi: 10.1016/j.jdcr.2016.10.005. eCollection 2016 Nov.
4
Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models.二甲双胍与普萘洛尔联合用药可预防不同乳腺癌模型中的癌症进展和转移。
Oncotarget. 2017 Jan 10;8(2):2874-2889. doi: 10.18632/oncotarget.13760.
5
Immunological consequences of immunization with tumor lysate vaccine and propranolol as an adjuvant: A study on cytokine profiles in breast tumor microenvironment.以肿瘤裂解物疫苗和普萘洛尔作为佐剂进行免疫接种的免疫后果：关于乳腺肿瘤微环境中细胞因子谱的研究
Immunol Lett. 2017 Jan;181:63-70. doi: 10.1016/j.imlet.2016.11.014. Epub 2016 Nov 27.
6
Propranolol induced G0/G1/S phase arrest and apoptosis in melanoma cells via AKT/MAPK pathway.普萘洛尔通过AKT/MAPK途径诱导黑色素瘤细胞发生G0/G1/S期阻滞和凋亡。
Oncotarget. 2016 Oct 18;7(42):68314-68327. doi: 10.18632/oncotarget.11599.
7
Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.普萘洛尔使甲状腺癌细胞对维莫非尼的细胞毒性作用敏感。
Oncol Rep. 2016 Sep;36(3):1576-84. doi: 10.3892/or.2016.4918. Epub 2016 Jul 7.
8
Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study.普萘洛尔与长春碱节拍化疗协同联合有效治疗晚期血管肉瘤：一项从 bench 到 bedside 的研究
EBioMedicine. 2016 Apr;6:87-95. doi: 10.1016/j.ebiom.2016.02.026. Epub 2016 Feb 17.
9
The potential anticancer effect of beta-blockers and the genetic variations involved in the interindividual difference.β受体阻滞剂的潜在抗癌作用及个体差异中涉及的基因变异。
Pharmacogenomics. 2016;17(1):74-9. doi: 10.2217/pgs.15.152. Epub 2015 Dec 14.
10
Biomarker Analysis in a Phase II Study of Sunitinib in Patients with Advanced Melanoma.舒尼替尼治疗晚期黑色素瘤患者的II期研究中的生物标志物分析
Anticancer Res. 2015 Dec;35(12):6893-9.