Inhibition of human endometrial cancer cell growth in vitro and in vivo by somatostatin analog RC-160

Misako Mishima, Tetsu Yano, Haruko Jimbo, Naomi Yano, Yutaka Morita, Hiroyuki Yoshikawa, Andrew V. Schally, Yuji Taketani

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

OBJECTIVE: Our purpose was to investigate the effect of the somatostatin analog RC-160 on the growth of the HEC-1 human endometrial cancer cell line in vivo and in vitro. STUDY DESIGN: Nude mice bearing subcutaneous implanted HEC-1 tumors were treated for 25 days with RC-160 (100 μg/d) delivered by osmotic minipumps. In cultured HEC-1 cells radioreceptor assay of somatostatin was performed, and the expression of messenger ribonucleic acid for somatostatin receptor subtypes (somatostatin receptors 1-5) was analyzed by reverse transcription-polymerase chain reaction. The effects of RC-160 on epidermal growth factor-stimulated cell proliferation and tyrosine phosphorylation of epidermal growth factor receptor were examined by colorimetric assay and Western blotting, respectively. RESULTS: The treatment with RC-160 resulted in a significant decrease in tumor volume, tumor weight, and serum insulin-like growth factor I levels compared with those values in control animals. The presence of high-affinity somatostatin binding sites and the expression of somatostatin receptor 2 and somatostatin receptor 3 messenger ribonucleic acid were demonstrated in HEC-1 cells by radioreceptor assay and reverse transcription-polymerase chain reaction, respectively. Epidermal growth factor-stimulated proliferation of HEC-1 cells was inhibited by RC-160 in a dose-dependent manner. Western blotting revealed that epidermal growth factor-induced tyrosine phosphorylation of epidermal growth factor receptor was inhibited by RC-160, which suggests that the direct inhibitory effect of RC-160 on HEC-1 cell growth might be mediated in part by interference with epidermal growth factor receptor phosphorylation. CONCLUSION: These results indicate that somatostatin analog RC-160 inhibits the growth of HEC-1 human endometrial cancer cells, thus implying its potential clinical utility in treating endometrial cancer.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalAmerican journal of obstetrics and gynecology
Volume181
Issue number3
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Endometrial cancer
  • Growth factors
  • Nude mice
  • Somatostatin
  • Somatostatin analog

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

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