In vitro evaluation of the anticancer drug modulatory effect of hyaluronidase in human gastrointestinal cell lines.
In an attempt to establish whether the combination of anticancer drugs with hyaluronidase would result in enhanced cytotoxicity, we have tested a range of 6 continuous cell lines against 4 different chemotherapeutic drugs with or without the addition of various concentrations of the enzyme. Measurement of cytotoxic drug effects has been performed using the Bactec system, a new semiautomated radiometric technique. In only 15 of a total of 144 experiments (11%) was a significant hyaluronidase-mediated potentiation of the single agents' activity seen. In the large majority of experiments, the antiproliferative effect of the combined treatment was classified as additive or subadditive, while in 23% it was antagonistic. Evaluation of the drug modulatory mechanism of hyaluronidase suggested that the combined drug-hyaluronidase effects were independent of the nature of the drug, the exposure mode and the concentration of the enzyme employed. Among the various tumor cell lines tested there was a marked heterogeneity in the sensitivity to the combined effect (P less than 0.0001). In summary, we have not been able to confirm the promising results of early reports of in vitro and in vivo enhancement of the cytotoxicity of antitumor agents by hyaluronidase. Our data emphasize the need for further controlled clinical studies in order to prove or disprove this new therapeutic approach.
Scheithauer
W
W
Department of Gastroenterology and Hepatology II, Vienna University School of Medicine, Austria.
Temsch
E M
EM
Stefenelli
T
T
Lathan
B
B
D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D006821:Hyaluronoglucosaminidase