Effect of a cytotoxic analog of LH-RH (T-98) on the growth of estrogen-dependent MXT mouse mammary cancers

Correlations between growth characteristics and EGF receptor content of tumors

Karoly Szepeshazi, Andrew V Schally, Gabor Halmos, Balazs Szoke, Kate Groot, Attila Nagy

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Female BDF mice bearing estrogen-dependent MXT mouse mammary cancers were treated for 4 weeks with a cytotoxic analog of luteinizing hormone-releasing hormone (LH-RH), T-98 (agonist [D-Lys6]LH-RH linked to glutaryl-2(hydroxymethyl)anthraquinone). The effects of T-98 were compared to those of equimolar amounts of the cytotoxic moiety 2-(hydroxymethyl)anthraquinone hemiglutarate (G-HMAQ) and carrier LH-RH agonist [D-Lys6]LH-RH. Both T-98 and [D-Lys6]LH-RH significantly inhibited the growth of MXT cancers, but G-HMAQ had only a minor non-significant effect. Cytotoxic analog T-98 and the carrier [D-Lys6]LH-RH had similar inhibitory hormonal activities on the pituitary-gonadal axis, but T-98 caused a larger reduction in tumor volume and decreased proliferation characteristics such as mitotic activity and AgNOR numbers in tumor cells to a greater extent than the carrier. Tumor inhibition by T-98, [D-Lys6]LH-RH, and ovariectomy was connected with a significant decrease in binding capacity of EGF receptors in tumor cell membranes. The concentration of EGF receptors remained high in tumors that continued to enlarge in spite of treatment and in all control untreated tumors, even those of small size. Thus, the changes in EGF receptors are likely to be the result of the therapy. Treatment with T-98 caused a greater reduction in the binding capacity of EGF receptors in tumors than [D-Lys6]LH-RH. This could explain the higher inhibitory effect of the cytotoxic analog on tumor growth. Since radiolabeled T-98 was shown to accumulate in MXT cancers 3 hours after a subcutaneous injection, this indicates that specific targeting might play a role in the antitumor effect exerted by this cytotoxic analog.

Original languageEnglish
Pages (from-to)129-139
Number of pages11
JournalBreast Cancer Research and Treatment
Volume40
Issue number2
StatePublished - Sep 9 1996
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Gonadotropin-Releasing Hormone
Estrogens
Breast Neoplasms
Growth
Neoplasms
lysine(6)-glutaryl-2-(hydroxymethyl)anthraquinone LHRH
Ovariectomy
Subcutaneous Injections
Tumor Burden
Therapeutics
Cell Membrane
glutaryl-2-(hydroxymethyl)anthraquinone
ErbB Receptors

Keywords

  • AgNOR
  • Apoptosis
  • Cytotoxic compounds
  • EGF receptors
  • Experimental breast cancer
  • LH-RH agonist
  • Organ distribution

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Effect of a cytotoxic analog of LH-RH (T-98) on the growth of estrogen-dependent MXT mouse mammary cancers : Correlations between growth characteristics and EGF receptor content of tumors. / Szepeshazi, Karoly; Schally, Andrew V; Halmos, Gabor; Szoke, Balazs; Groot, Kate; Nagy, Attila.

In: Breast Cancer Research and Treatment, Vol. 40, No. 2, 09.09.1996, p. 129-139.

Research output: Contribution to journalArticle

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