Effects of the phosphodiesterase-IV inhibitor EMD 95832/3 on tumour growth and cachexia in rats bearing the Yoshida AH-130 ascites hepatoma.
Administration of the phosphodiesterase-IV inhibitor EMD 95832/3 (Merck KGaA, Darmstadt, Germany) to rats bearing the ascites hepatoma Yoshida AH-130, a highly cachectic tumour, could not prevent either the anorexia nor the massive weight loss (affecting both adipose and skeletal muscle tissues) present in the tumour-bearing animals. This compound did not have any effects on the fractional rates of protein turnover in skeletal muscle, and did not affect circulating triacylglycerols or lipoprotein lipase activity in adipose tissue. Although the administration of EMD 95832/3 did not influence tumour growth either, it did increase the number of tumour cells undergoing apoptosis. It is concluded that the drug is unable to reverse the cachectic state in this particular experimental tumour model.
Meijsing
Bas
B
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain.
Carbó
Neus
N
López-Soriano
Francisco J
FJ
Argilés
Josep M
JM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000201:enzymology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D019344:Lactic Acid / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012517:Sarcoma, Yoshida / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D010726:Phosphodiesterase Inhibitors; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D008071:Lipoprotein Lipase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D000409:Alanine