Antineoplastic effects of octreotide on human gallbladder cancer cells in vitro.
OBJECTIVE
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-G(1) peaks in the octreotide group, significantly higher than the control group (P=0.013). There was also an augmentation in the cell proportion of G(0)/G(1) phase (P=0.015), while the proportion of S phase and G(2)/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).


CONCLUSIONS
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.
Wang
Jing-Hua
JH
ICU of Beijing Hospital, Beijing 100730, China. wjh6333@sina.com
Xing
Quan-Tai
QT
Yuan
Meng-Biao
MB
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005706:Gallbladder Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D015282:Octreotide / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015282:Octreotide