Endocrine Abstracts

Hepatocellular carcinoma (HCC) is often diagnosed at late stage or metastatic condition. Surgical resection is considered treatment of choice and other treatment options include chemoembolization, radiofrequency ablation and photodynamic therapy. We evaluated the expression levels of the 5 somatostatin receptors (SSTRs) in 23 biopsies of HCC patients and also mTOR, p70S6K and 4eBP1 in HuH-7 and HepG2 and investigated the in vitro effect of somatostatin analogs (SA) and mTOR inhibitors on cell proliferation. The receptor expression was assessed by RT-qPCR and sstr2 and 5 localization by ICC. The proliferation was tested using DNA assay. Sstr2>sstr1>sstr5 were expressed in the patients. Cell lines showed the presence dell’sstr1, 2, and 5 as well as mTOR, p70S6K, 4eBP1. ICC showed a heterogeneous localization of sstr5 and sstr2 in Hep-G2 and Huh-7. Octreotide showed a no significant dose-dependent inhibitory effect in both cell lines. Bim23244 induced a significant inhibitory effect (18.2%, P=0.02) in HepG2 at 10⁻⁷ M and Bim23926 16.4% (P=0.00) at 10⁻⁷ M in Huh-7. Incubation with mTOR inhibitors resulted in a dose-dependent growth inhibition in both cell lines. Octreotide has not synergistic or additive effect with rapamycin at high concentration, but when it was used in combination with rapamycin at low concentration was able to revert the antiproliferative effect of rapamycin in HepG2 and HuH-7. This effect was also associated to an hyperexpression of sstr2 and 5 and upregulation of pERK1/2. Our data provide evidence of sstrs expression in HCC but other studies will be required to justify the clinical use of these compounds in the treatment of advanced HCC. mTOR inhibitors have an essential growth inhibitory effect in HCC cell line, even though in vitro the rapamycin effect can be reverted by octreotide, showing that HCCs do not act as a typical neuroendocrine tumor.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.