Differences of Therapeutic Efficacy Between Different Kinds of Somatostatin Analogue for Primary Hepatocellular Carcinoma

Abstract

To explore the effects of SOM230, octreotide and lanreotide on hepatocellular carcinoma cell line Bel-7402 In vivoand In vitro, and to analyze the differences of their therapeutic efficacy with relevant mechanisms. Methods At different time points (24, 48, 72 h), the cell counting kit-8 (CCK8) was used to evaluate cell proliferation (drug concentration 1×10-10-1×10-5mol/L) and the Annexin Ⅴ-FITC/PI staining was used to assess cell apoptosis (drug concentration 1×10-5mol/L), while the real-time quantitative PCR was used to detect cellular SSTRexpression changes before and after interventions. A transplanted tumor model was set up, and the tumor-bearing nude mice were treated by three drugs with a common dose of 100 μg/（kg·d） or same volume of normal saline, respectively. After a treatment period of 6 weeks, real-time quantitative PCR and Western blot test were performed to detect the expression changes ofSSTR in tumor tissues from the level of gene and protein. Results All three drugs could inhibit the cell proliferation of Bel-7402. However, they were unable to promote the cell apoptosis. In vitro, the expressions ofSSTR1, SSTR4genes did not change over time in each group. The expressions ofSSTR2gene were decreased in three intervention groups while the expressions ofSSTR5gene were increased first and then decreased. Compared with the control group, all differences have statistical significance (PIn vivo, the expression ofSSTR1gene in SOM230 group was increased when compared with that of the other groups; the expressions ofSSTR2gene in three intervention groups were increased when compared with that of the control group; the expressions of SSTR5gene in SOM230 group and lanreotide group were increased when compared with that of the octreotide group and the control group, and all differences have statistical significance (P<0.05). The Western blot test confirmed these results from the protein level. Conclusion In a certain concentration range, the long-term treatment of SSTA with high affinities to SSTR2 and SSTR5 could inhibit the growth of HCC.

Keywords: Somatostatin, Liver cancer, Bel-7402 cells, Xenografts