Pre-clinical study of BK-UM, a novel inhibitor of HB-EGF, for ovarian cancer therapy

Anticancer Res. 2014 Aug;34(8):4615-20.

Abstract

Background/aim: Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor family, is a target for ovarian cancer therapy. The present study investigated the administration schedule of BK-UM, an anticancer agent targeting HB-EGF.

Materials and methods: The ovarian cancer cell line, RMG-I, was injected subcutaneously into five-week-old female nude mice. The BK-UM was administered intraperitoneally, using three administration schedules with different doses. The tumor volume was calculated every week. Statistical significance was assessed using the Mann-Whitney U-test.

Results: At doses >0.1 mg/kg, BK-UM displayed significant antitumor effects, although the antitumor effects and body weights of mice did not significantly differ by dose or by three different administration schedules. At a dose <0.1 mg/kg, however, BK-UM had little inhibitory effect on tumor growth.

Conclusion: Daily administration of BK-UM, which has a potentially dose-dependent antitumor effect, may be the optimal schedule for clinical application.

Keywords: BK-UM (CRM197); HB-EGF; ovarian cancer; preclinical study.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bacterial Proteins / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Female
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • CRM197 (non-toxic variant of diphtheria toxin)