دورية أكاديمية
أعرض في EDS

Clusterin inhibition using OGX-011 synergistically enhances antitumour activity of sorafenib in a human renal cell carcinoma model.

التفاصيل البيبلوغرافية
العنوان: Clusterin inhibition using OGX-011 synergistically enhances antitumour activity of sorafenib in a human renal cell carcinoma model.
المؤلفون: Kususda Y; Division of Urology, Kobe University Graduate school of Medicine, Chuo-ku, Japan., Miyake H, Gleave ME, Fujisawa M
المصدر: British journal of cancer [Br J Cancer] 2012 Jun 05; Vol. 106 (12), pp. 1945-52. Date of Electronic Publication: 2012 May 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.
مواضيع طبية MeSH: Benzenesulfonates/*pharmacology , Carcinoma, Renal Cell/*drug therapy , Clusterin/*antagonists & inhibitors , Kidney Neoplasms/*drug therapy , Pyridines/*pharmacology , Thionucleotides/*pharmacology, Animals ; Apoptosis/drug effects ; Benzenesulfonates/administration & dosage ; Benzenesulfonates/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Clusterin/metabolism ; Disease Models, Animal ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Niacinamide/analogs & derivatives ; Oligonucleotides, Antisense/pharmacology ; Phenylurea Compounds ; Pyridines/administration & dosage ; Pyridines/therapeutic use ; Sorafenib ; Thionucleotides/administration & dosage ; Up-Regulation ; Xenograft Model Antitumor Assays
مستخلص: Background: The objective of this study was to investigate whether the therapeutic activity of sorafenib could be enhanced by combining with OGX-011, an antisense oligodeoxynucleotide (ODN) targeting clusterin, in renal cell carcinoma (RCC).
Methods: We investigated the effects of combined treatment with OGX-011 and sorafenib on a human RCC ACHN model both in vitro and in vivo.
Results: Although clusterin expression was increased by sorafenib, additional treatment of ACHN with OGX-011 significantly blocked the upregulation of clusterin induced by sorafenib. Despite the lack of a significant effect on the growth of ACHN, OGX-011 synergistically enhanced the sensitivity to sorafenib, reducing the IC(50) by >50%. Apoptotic changes were intensively detected in ACHN after combined treatment with OGX-011 and a sublethal dose of sorafenib, but not either agent alone. Furthermore, this combined treatment resulted in the marked downregulation of phosphorylated Akt and p44/42 mitogen-activated protein kinase in ACHN compared with treatment with either agent alone. In vivo systemic administration of OGX-011 plus sorafenib significantly decreased the ACHN tumour volume compared with control ODN plus sorafenib.
Conclusion: Combined use with OGX-011 may be useful in enhancing the cytotoxic effect of sorafenib on RCC by inducing apoptosis and inactivating major signal transduction pathways.
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المشرفين على المادة: 0 (Benzenesulfonates)
0 (Clusterin)
0 (OGX-011)
0 (Oligonucleotides, Antisense)
0 (Phenylurea Compounds)
0 (Pyridines)
0 (Thionucleotides)
25X51I8RD4 (Niacinamide)
9ZOQ3TZI87 (Sorafenib)
تواريخ الأحداث: Date Created: 20120517 Date Completed: 20120807 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3388571
DOI: 10.1038/bjc.2012.209
PMID: 22588555
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-1827
DOI:10.1038/bjc.2012.209