d-phenylalanyl-cysteinyl-tyrosyl-tryptophyl-lysyl-cysteinyl-threoninamide and Liver-Neoplasms

Clinical resistance to chemotherapeutic drugs is an important problem in the treatment of cancer; the circumvention of resistance has become one of the basic goals of cancer therapy. The most frequent form of primary liver cancer is hepatocellular carcinoma, which is essentially refractory to chemotherapy. We earlier showed that TT-232, a new somatostatin analogue developed in our laboratory, exerted a strong antiproliferative effect both in vitro and in vivo, but no growth hormone release inhibitory or antisecretory activity. Here we report that TT-232 has a pronounced antiproliferative effect on differentiated and dedifferentiated, drug-sensitive and multidrug-resistant hepatocellular carcinoma cell lines. TT-232 induces apoptosis at comparable levels in all these hepatoma variants demonstrating that the multidrug resistance of hepatomas does not correlate with a reduced susceptibility to apoptosis induction. These results clearly reveal that the machinery involved in apoptosis is functional in both drug-sensitive and resistant hepatoma variants and can be activated by the somatostatin analogue TT-232.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Differentiation; Cell Division; Drug Resistance, Multiple; Humans; Liver Neoplasms; Peptides, Cyclic; Somatostatin; Tumor Cells, Cultured