| Delineation of apoptotic genes for synergistic apoptosis of lexatumumab and anthracyclines in human renal cell carcinoma cells by polymerase chain reaction array. | |
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MedLine Citation:
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PMID: 22205156 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Lexatumumab, a human agonistic monoclonal antibody against tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor-2 (TRAIL-R2), is a promising molecular-targeted therapeutic agent. Our past study indicated that low concentrations of doxorubicin sensitized renal cell carcinoma (RCC) cells to lexatumumab-mediated apoptosis. The present study was designed to examine the cellular and molecular effects of lexatumumab and anthracyclines in RCC cells. The treatment of human RCC cells with lexatumumab in combination with anthracyclines, epirubicin, and pirarubicin had a synergistic cytotoxicity. A marked synergistic apoptosis was induced by lexatumumab in combination with epirubicin or pirarubicin. Epirubicin and pirarubicin significantly increased the TRAIL-R2 expression at both the mRNA and the protein levels. The combination-induced cytotoxicity was significantly suppressed by the human recombinant DR5:Fc chimeric protein. To further explore the molecular mechanisms in this synergistic cytotoxicity with lexatumumab and anthracyclines, the changes in 84 apoptosis-related genes were evaluated by a quantitative polymerase chain reaction (PCR) array. Among these genes, 18 (CD40LG, FASLG, LTA, TNSF7, FAS, BAG3, BAK1, BAX, BID, BIK, BCL10, caspase-1, caspase-5, caspase-6, caspase-10, TNF receptor-associated factor 1, PYCARD, and CIDEA) were significantly upregulated and eight (TNF receptor-associated factor 4, TNFRSF11B, TNF, BCL2, BCL2L1, BNIP3L, caspase-9, and DAPK1) were downregulated at mRNA levels in RCC cells cotreated with lexatumumab and epirubicin. Furthermore, the upregulation of mRNA levels of PYCARD and CIDEA was confirmed using real-time reverse transcriptase-PCR analysis. The present study demonstrates that anthracylines sensitize RCC cells to lexatumumab-mediated apoptosis by inducing TRAIL-R2 expression, and the utility of PCR array to elucidate the mechanism of synergistic apoptosis. |
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Authors:
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Xinghua Jin; Xiu-Xian Wu; Chenglou Jin; Masashi Inui; Mikio Sugimoto; Yoshiyuki Kakehi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-25 |
Journal Detail:
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Title: Anti-cancer drugs Volume: - ISSN: 1473-5741 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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aQiqihar Medical University, Qiqihar 161006, China bDepartment of Urology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan cDepartment of Urology, Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China. |
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