Interleukin-1α synergistic in vivo enhancement of cyclophosphamide- and carboplatin-mediated antitumor activity |
| |
Authors: | Wei-Dong Yu Ming-Jei Chang Donald L Trump C S Johnson |
| |
Institution: | (1) Department of Otolaryngology, University of Pittsburgh School of Medicine, 203 Lothrop Street, Room 110, Pittsburgh, PA 15213, USA Tel: (412) 647-6224; Fax: (412) 647-8720 e-mail: candacej@.vms.cis.pitt.edu, US;(2) Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, US;(3) Department of Pharmacology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, US |
| |
Abstract: | Interleukin-1α (IL-1α) has potent acute antitumor activity in vivo and can enhance the efficacy of chemotherapeutic drug-mediated
antitumor responses. Studies were undertaken to examine the ability of IL-1α to enhance the activity of cyclophosphamide (CTX)
administered in combination with carboplatin. To determine the in vivo effect of IL-1α, CTX and/or carboplatin, mice bearing
14-day RIF-1 tumors were treated on day 0 with a concurrent i.p. injection of varying doses of CTX (5–150 mg/kg), human IL-1α
(125 μg/kg), and carboplatin (50 mg/kg) and examined 24 h later for the surviving fraction by the in vivo excision clonogenic-tumor-cell
assay. Even at the lowest doses of CTX, IL-1α significantly enhanced the clonogenic tumor cell kill when compared to treatment
with CTX alone. When carboplatin was added to the treatment schema, significantly greater clonogenic cell killing and tumor
regrowth delay were observed as compared to any agent alone or a two-drug combination (CTX/IL-1α or CTX/carboplatin). Significant
enhancement was observed even at low doses of CTX in combination with carboplatin and IL-1α. The interaction between the three-drug
combination was found to be synergistic as determined by the median dose effect with significant dose reduction apparent for
IL-1α and CTX when used in this combination. These results demonstrate that IL-1α can synergistically enhance the antitumor
efficacy of CTX and the combination of CTX and carboplatin.
Received: 11 September 1996 / Accepted: 20 May 1997 |
| |
Keywords: | Antitumor Cyclophosphamide Carboplatin Interleukin-1α Synergistic |
本文献已被 SpringerLink 等数据库收录! |
|