Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia.
Insulin-like growth factor I (IGF-I) has been implicated in the regulation and maintenance of skeletal muscle protein balance and thus may be of potential benefit in attenuating the cancer-cachectic process. To examine this hypothesis, 47 sham or tumor-implanted Fischer 344 rats were randomized to receive either continuous subcutaneous IGF-I (220 or 400 micrograms/day) or saline as control. In the tumor-bearing (TB) population, IGF-I-treated groups showed a dose-dependent increase in host weight gain (P less than 0.05), final carcass weight (P less than 0.05), and gastrocnemius muscle weights (P less than 0.05) and protein contents (0.50 +/- 0.02, 0.40 +/- 0.01, and 0.52 +/- 0.03 g/100 g host wt, for non-TB saline, TB saline, and TB 400 mg IGF-I groups, respectively; P less than 0.01, IGF-I vs. saline). Similar increases in muscle RNA and DNA contents (P less than 0.01) were induced by IGF-I treatment (P less than 0.05). IGF-I treatment in this rat sarcoma model significantly reduced the proportion of aneuploid cells in the tumor (aneuploid-to-diploid ratio: TB saline 1.1 +/- 0.2 vs. TB IGF-I 0.5 +/- 0.1; P less than 0.05). IGF-I treatment attenuated host muscle protein and lean tissue depletion without stimulation of tumor growth. The tumor aneuploid population was reduced in response to IGF-I treatment. Thus IGF-I may be a potential therapeutic agent in cancer-induced cachexia.
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EH
Department of Surgery, New York Hospital-Cornell Medical Center, New York 10021.
Rock
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CS
Lazarus
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Stiaino-Coico
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Moldawer
L L
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Lowry
S F
SF
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology*; D002453:Cell Cycle; D004247:DNA / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D004435:Eating; D005434:Flow Cytometry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D009132:Muscles / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D011003:Ploidies; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000473:pathology / Q000503:physiopathology*; D015430:Weight Gain
D001786:Blood Glucose; D004273:DNA, Neoplasm; D011506:Proteins; D011994:Recombinant Proteins; D012313:RNA; D007334:Insulin-Like Growth Factor I; D004247:DNA