LH-RH receptors in human colorectal cancers: Unexpected molecular targets for experimental therapy

Karoly Szepeshazi, Andrew V. Schally, Gabor Halmos

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Since the efficacy of chemotherapy can be enhanced by targeting to specific receptors on tumors, we investigated the expression of LH-RH receptors in 5 human colon cancer lines and the effects of cytotoxic LH-RH analogs on these tumors. Nude mice bearing HT-29, HCT-116, HCT-15, LoVo and Colo-320DM cancers were treated with cytotoxic LH-RH analogs AN-152 and AN-207 or their respective cytotoxic radicals doxorubicin (DOX) and 2-pyrrolino-DOX (AN-201). The reduction in tumor growth was evaluated, and cell proliferation characteristics as well as apoptosis were analyzed by histological methods. LH-RH receptors on the tumors were investigated by radioligand binding assays and their mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). All 5 colorectal cancer lines expressed high affinity binding sites for LH-RH, and mRNA for the LH-RH receptors. Both cytotoxic LH-RH analogs AN-152 and AN-207 powerfully inhibited growth of all colon cancers. AN-207 had the strongest effect on HT-29 and HCT-116 tumors, and AN-152 was the most effective on Colo-320DM cancers. Cytotoxic radicals AN-201 and DOX were less effective on these 3 tumors, but had effects similar to AN-152 and AN-207 on HCT-15 and LoVo carcinomas. The four cytotoxic compounds also differently affected apoptosis and proliferation rate of the various tumor lines. Our findings suggest that cytotoxic LH-RH analogs should be considered for the therapy of patients with advanced colorectal carcinoma.

Original languageEnglish (US)
Pages (from-to)1485-1492
Number of pages8
JournalInternational journal of oncology
Volume30
Issue number6
StatePublished - Jun 1 2007

Keywords

  • Colorectal cancer
  • Cytotoxic LH-RH analog
  • LH-RH receptor
  • Targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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