Abstract
BACKGROUND/PURPOSE: We investigated the in vitro and in vivo inhibitory effects of a somatostatin analogue (octreotide, OCT) on cholangiocarcinoma cell lines.
METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect the gene expression of five somatostatin receptor (SSTR) subtypes in four cholangiocarcinoma cell lines (RBE, NEC, QBC939, and SSP-25). The antiproliferative effects of OCT on these cell lines were determined by means of an MTT assay in vitro, as well as in a nude mouse tumor heterograft model in vivo. Apoptosis and cell cycles in the cholangiocarcinoma cell lines after OCT administration were evaluated by flow cytometry; and the effects of OCT on the expression of cyclin E, cyclin-dependent kinase 2 (CDK2), and p27kipl were evaluated by Western blots.
RESULTS: Only SSTR2 mRNA was detected in these four cholangiocarcinoma cell lines. OCT significantly inhibited the proliferation of the four cholangiocarcinoma cell lines in vitro ( P < 0.05 vs control), and the weights of the QBC939 xenografts in the OCT-treated group were lower than those in the control group, but there was no significant difference between them. After 48-h exposure to 10(3) ng/ml OCT, flow cytometric analysis demonstrated an increased number of cells in G0/G1 phase associated with a decreased number of cells in G2/M and S phases ( P < 0.01 vs control). Apoptosis was not observed in any samples. The expression of p27kipl was promoted by OCT administration, while that of cyclin E and that of CDK2 were inhibited.
CONCLUSIONS: The results proved that OCT inhibits the proliferation of cholangiocarcinoma cells through G0/G1 cell cycle arrest rather than through the process of apoptosis. These effects are partially mediated by enhancing the expression of p27kipl, and decreasing the amounts of cyclin E-CDK2 complex.
See also:
- Somatostatin in oncology, the overlooked evidences;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Neuroblastoma: Complete objective response to biological treatment;
- Complete objective response to biological therapy of plurifocal breast carcinoma.