Effect of Octreotide on Apoptosis-related Proteins in Rat Kupffer Cells: A Possible Anti-tumour Mechanism

• Published in: Anticancer research Vol. 24; no. 2B; pp. 833 - 841
• Main Authors: XIDAKIS, Costas, KOLIOS, George, VALATAS, Vassilis, NOTAS, George, MOUZAS, Ioannis, KOUROUMALIS, Elias
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-03-2004
• Subjects: Animals; Antineoplastic Agents, Hormonal - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; bcl-2-Associated X Protein; bcl-X Protein; Biological and medical sciences; Caspase 3; Caspases - blood; Gene Expression - drug effects; Kupffer Cells - cytology; Kupffer Cells - drug effects; Kupffer Cells - metabolism; Lipopolysaccharides - pharmacology; Male; Medical sciences; Octreotide - pharmacology; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tumors; Antineoplastic agent; Rat; Peptide hormone; Rodentia; Kupffer cells; Octreotide; Neuropeptide; Protein; LPS; Kupffer cell; Vertebrata; Mammalia; Cancerology; Analog; Animal; Lipopolysaccharide; Somatostatin; Tumor cell; Apoptosis
• ISSN: 0250-7005; 1791-7530

Background: Octreotide may prolong survival in patients with hepatocellular carcinoma, through an as yet unidentified mechanism.
Kupffer cells play a key role in antitumour activity. Kupffer cell apoptosis is of major importance for the maintenance of
this antitumour activity. Materials and Methods: We studied the in vitro effects of octreotide in the RNA expression of apoptotic
and antiapoptotic proteins in isolated rat Kupffer cells, before and after exposure to lipopolysaccharide (LPS). Apoptotic
and antiapoptotic gene expression was assessed using a semi-quantitative multiplex RT-PCR measuring bax, bcl-xS, bcl-2 and
bcl-xL. LICE (caspase-3) mRNA was used as a measure of apoptosis. Results: Unstimulated Kupffer cells exhibited increased
proapoptotic gene expression in a time-dependent manner, paralleled by a similar increase of LICE. LPS stimulation decreased
the expression of proapoptotic bax and bcl-xS mRNA without effecting the antiapoptotic proteins. A decrease of LICE expression
became significant at 48 hours. Octreotide showed a reduction of proapoptotic proteins, accompanied by an early increase and
a late reduction of antiapoptotic proteins and a net decrease of LICE expression. A combination of LPS and octreotide produced
a similar effect with the exception of a late increase of LICE expression, probably caused by a late increase of bax and bcl-xS.
Conclusion: LPS and octreotide reverse the observed increased apoptosis of cultured Kupffer cells by influencing both proapoptotic
and antiapoptotic proteins. Therefore, the antitumour effect of octreotide in hepatocellular carcinoma may, in part, be explained
by its antiapoptotic effect on Kupffer cells.