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Journal of Hepato-Biliary-Pancreatic Surgery

, Volume 9, Issue 4, pp 497–502 | Cite as

Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment

  • Bo Zhao
  • Hua Zhao
  • Na Zhao
  • Xue-guang Zhu

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.

Key words Cholangiocarcinoma Somatostatin Cell cycle Cyclins 

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Copyright information

© Springer-Verlag Tokyo 2002

Authors and Affiliations

  • Bo Zhao
    • 1
  • Hua Zhao
    • 1
  • Na Zhao
    • 1
  • Xue-guang Zhu
    • 1
  1. 1.Department of General Surgery, People's Hospital, Peking University, XiZhiMenNan Street 11#, Beijing 100044, ChinaCN

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