Antineoplastic effects of octreotide on human gallbladder cancer cells in vitro

doi:10.3748/wjg.v10.i7.1043

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Research

World J Gastroenterol. Apr 1, 2004; 10(7): 1043-1046
Published online Apr 1, 2004. doi: 10.3748/wjg.v10.i7.1043

Antineoplastic effects of octreotide on human gallbladder cancer cells in vitro

Jing-Hua Wang, Quan-Tai Xing, Meng-Biao Yuan

Jing-Hua Wang, ICU of Beijing Hospital, Beijing 100730, China

Quan-Tai Xing, Meng-Biao Yuan, Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China

Author contributions: All authors contributed equally to the work.

Correspondence to: Dr. Jing-Hua Wang, ICU of Beijing Hospital, Beijing 100730, China. wjh6333@sina.com

Telephone: +86-10-65132266-6412

Received: October 31, 2003
Revised: November 11, 2003
Accepted: December 8, 2003
Published online: April 1, 2004

Abstract

AIM: To investigate whether octreotide can inhibit the growth of human gallbladder cancer cells in vitro and to elucidate the antineoplastic mechanism of octreotide in gallbladder cancer.

METHODS: A human gallbladder cancer cell line, GBC-SD, was cultured in vitro. The antiproliferative effects of octreotide were examined by means of an MTT assay and a colony forming ability assay. Morphological variation was investigated under scanning electron microscopy and transmission electron microscopy. Cell cycle analysis and apoptosis rate was evaluated by flow cytometry (FCM) after staining by propidium iodide. DNA fragmentation was assayed by agarose gel electrophoresis. Immunohistochemical staining was performed to evaluate the expressions of mutant-type p53 and bcl-2.

RESULTS: The growth curve and colony forming ability assay showed significant inhibition of octreotide to the proliferation of GBC-SD cells in culture in a time- and dose-dependent manner. After exposure to octreotide, GBC-SD cells showed typically apoptotic characteristics, including morphological changes of chromatin condensation, vacuolar degeneration, nucleus fragmentation and apoptotic body formation. In FCM profile apoptotic cells showed increased sub-G₁ peaks in the octreotide group, significantly higher than the control group (P = 0.013). There was also an augmentation in the cell proportion of G₀/G₁ phase (P = 0.015), while the proportion of S phase and G₂/M phase remained unchanged (P = 0.057 and P = 0.280, respectively). DNA agarose gel electrophoresis displayed a ladder after exposure to 1 000 nmol/L octreotide. After being treated with octreotide, the expressions of both mutant-type p53 and bcl-2 decreased considering the percentage of positive cells (P < 0.05).

CONCLUSION: Octreotide has a negative action to the proliferation of GBC-SD cells, and the mechanism may be related to cytostatic and cytotoxic effects. The reduction of mutant-type p53 and bcl-2 expressions may be associated with the apoptosis induced by octreotide.

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