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


METHODS
Nude mice bearing subcutaneous implanted HEC-1 tumors were treated for 25 days with RC-160 (100 microgram/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.


CONCLUSIONS
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.
Mishima
M
M
Department of Obstetrics, Faculty of Medicine, University of Tokyo, Japan.
Yano
T
T
Jimbo
H
H
Yano
N
N
Morita
Y
Y
Yoshikawa
H
H
Schally
A V
AV
Taketani
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D017481:Receptors, Somatostatin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C051458:vapreotide; D013004:Somatostatin; D004815:Epidermal Growth Factor