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 103 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.
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Received: March 31, 2002 / Accepted: June 26, 2002
Acknowledgments. The authors thank Professor Ben-li Han and Dr. Munechika Enjoji for providing valuable human cholangiocarcinoma cell lines.
Offprint requests to: X.-G. Zhu
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Zhao, B., Zhao, H., Zhao, N. et al. Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment. J Hep Bil Pancr Surg 9, 497–502 (2002). https://doi.org/10.1007/s005340200062
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DOI: https://doi.org/10.1007/s005340200062