Treatment Of Liver Cancer In Mice By The Intratumoral Injection Of An Octreotide-Based Temperature-Sensitive Gel

Octreotide (OCT) can inhibit tumor growth with few side-effects. In this study, we hypothesized that an OCT- and poloxamer 407 (P407)-based temperature-sensitive gel may compensate for the short half-life of OCT, which may thus lead to the development of a novel therapy for patients with end-stage liver cancer by intratumoral injection. The proliferation and apoptosis of mouse Hca-F hepatocellular carcinoma cells were determined by MTT assay and Annexin V-PI staining. A mouse model of hepatocellular carcinoma was established by the subcutaneous transplantion of Hca-F cells and OCT-P407 or OCT solution were injected into the tumors, followed by the detection of OCT levels by high performance liquid chromatography (HPLC) over a specific time period. OCT-P407, ethanol, OCT, P407 or normal saline (NS) were injected into the tumors and the tumor size, weight and inhibition rate were measured 8 days later. Additionally, the expression of somatostatin receptor-2 (SSTR-2), vascular endothelial growth factor (VEGF) and caspase-3 was detected by immunohistochemistry and RT-PCR. Compared with the OCT group, the tumor inhibition rate and the apoptotic rate in the OCT-P407 group were higher and the effects were longer. The tumor size and weight in the OCT-P407 group were lower and the tumor inhibition rate higher compared with the OCT, P407 and NS groups, with the exception of the ethanol group. The protein and mRNA expression of SSTR-2 and caspase-3 in the OCT-P407 group was higher, and that of VEFG was lower compared with the other groups, with the exception of the ethanol group. In the present study, we demonstrate that the intratumoral injection of OCT-P407 maintains OCT local effective concentration and prolongs its action time, with a greater therapeutic effect than that of OCT on its own. Although ethanol is more effective in certain aspects, its tumor inhibitory effects are similar to OCT-P407 and as such, OCT-P407 may be a suitable alternative.