The influence of recombinant human insulin-like growth factor-I (rhIGF- I) on cell growth and cytotoxicity of drugs in childhood rhabdomyosarcoma cell lines and xenograft models

Corrie E.M. Gidding, Glen S. Germain, Michael B. Dilling, Tiny G.J. Meeuwsen-de Boer, Richard A. Ashmun, Siebold S.N. De Graaf, Karen A. Veverka, Willem A. Kamps, Peter J. Houghton

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Purpose: Recombinant human insulin-like growth factor I (rhIGF-I) has been reported to ameliorate vincristine-induced neuropathy, the dose-limiting side effect of this antimitotic anticancer drug. However, rhIGF-I also might have adverse effects, as has been shown in vitro, where it stimulates growth of cancer cells and protects them from cytotoxicity of anticancer drugs. The influence of rhIGF-I on the cytotoxicity of vincristine has not yet been studied. Furthermore, studies performed have been done under serum-free conditions, which are far from physiological. Methods: We studied the influence of rhIGF-I on the growth of two rhabdomyosarcoma cell lines (Rh30 and Rh1) and on the antitumor effects of vincristine, cisplatin, etoposide, doxorubicin, and topotecan under serum-free and serum-containing conditions. To extend the in vitro data, we grew Rh30 cells as xenografts in mice and determined the effects of vincristine, rhIGF-I or their combination on tumor growth. Results: In vitro, both cell lines demonstrated a functional type I IGF receptor, as shown by the rapid activation of ribosomal p70 S6 kinase after stimulation with rhIGF-I. Under serum-free conditions, rhIGF-I stimulated growth of both cell lines. Exposure to cytotoxic drugs with and without rhIGF-I resulted in higher cell numbers in cultures exposed to rhIGF- I. However, relative to the appropriate control, fractional growth inhibition and or cell kill of the cytotoxic drugs was identical with and without rhIGF- I. Under serum-containing conditions, rhIGF-I had no effect on cell growth or drug cytotoxicity. In vivo we did not find a significant influence of rhIGF-I on HxRh30 cell growth, or on the antitumor activity of vincristine. Conclusions: These studies show that rhIGF-I has no adverse effects on human rhabdomyosarcoma growth or on the antitumor effect of cytotoxic drugs under serum-containing conditions in vitro or in tumor-bearing mice. Potentially, therefore, rhIGF-I may ameliorate vincristine-induced neuropathy without adversely influencing tumor growth or vincristine cytotoxicity in children.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Cytotoxicity
  • IGF-I
  • Vincristine

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'The influence of recombinant human insulin-like growth factor-I (rhIGF- I) on cell growth and cytotoxicity of drugs in childhood rhabdomyosarcoma cell lines and xenograft models'. Together they form a unique fingerprint.

Cite this