Linker-based GnRH-PE chimeric proteins inhibit cancer growth in nude mice |
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Authors: | Ahmi Ben-Yehudah Shai Yarkoni Amotz Nechushtan Ruth Belostotsky Haya Lorberboum-Galski |
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Affiliation: | (1) Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel;(2) Present address: Biochemistry Section, Surgical Neurology Branch, National Institute of Health, Bethesda, Maryland, USA |
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Abstract: | Since the number of cancer-related deaths has not decreased in recent years, major efforts are being made to find new drugs for cancer treatment. In this report we introduce the gonadotropin releasing hormone-Pseudomonas exotoxin (GnRH-PE) based chimeric proteins L-GnRH-PE66 and L-GnRH-PE40. These proteins are composed of a GnRH moiety attached to modified forms ofPseudomonas exotoxin via a polylinker (gly4ser)2. The chimeric proteins L-GnRH-PE66 and L-GnRH-PE40 have the ability to target and kill adenocarcinoma cell linesin vitro, whereas non-adenocarcinoma cell lines are not affected. We demonstrate that L-GnRH-PE66 and L-GnRH-PE40 efficiently inhibit cancer growth. Nude mice were injected subcutaneously with the SW-48 adenocarcinoma cell line to produce xenograft tumours. When the tumours were established and visible, the animals were injected with chimeric proteins for 10 days. At the end of this period, a reduction of up to 3-fold in tumor size was obtained in the treated mice, as compared with the control group, which received equivalent amounts of GnRH; the difference was even greater 13 days after termination of treatment. Thus, the chimeric proteins L-GnRH-PE66 and L-GnRH-PE40 are promising candidates for treatment of a variety of adenocarcinomas and their use in humans should be considered. |
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Keywords: | Gonadotropin releasing hormone (GnRH) Pseudomonas exotoxin A (PE) cancer chimeric proteins targeting |
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