Aim: To study the effect of octreotide on cell proliferation and apoptosis in different hepatocellular carcinoma (HCC) cells and hepatocytes.
Methods: The proliferation of HCC cells (HepG2, SMMC-7721) and hepatocytes (L-02) was determined by MTT assay. Apoptosis was detected either by fluorescent staining, transmission electron microscopy or flow cytometry. The content of AFP in the supernatant of cultured HCC cells was determined by electrochemiluminescence immunoassay. The expression of SSTR subtypes was identified by RT-PCR.
Results: The proliferation of HCC cells and L-02 cells was inhibited significantly by octreotide (0.25, 0.5, 1.0, 2.0 and 4.0 mg/L). However, the apoptosis of HCC cells markedly increased in a concentration-dependent manner. Both the apoptosis index and the percentage of apoptotic cells in L-02 cells were significantly lower than those of HepG2 and SMMC-7721 cells. The content of AFP in the supernatant of cultured HepG2 cells treated with octreotide was also statistically reduced. Furthermore, SSTR2 and SSTR4 were positive in both the hepatocellular carcinoma cells and in the L-02 cells. SSTR3 was only expressed in the two heptatocellular carcinoma cells, and SSTR5 was found in the SMMC-7721 cells. No SSTR1 was detected either in HCC cells or L-02 cells.
Conclusions: Apoptosis induction is a major mechanism of octreotide inhibition on hepatocellular cells. SSTR3 is expressed in the HCC cells, but not in the L-02 cells, which suggests a molecular basis for the HCC-selective effects of octreotide.
Copyright 2004 Acta Pharmacologica Sinica