Inhibitory effects of octreotide in combination with adeno-associated virus-mediated melanoma differentiation-associated gene-7 on hepatocellular carcinoma

Abstract

Objective To determine the inhibitory effects of octreotide of various dosages in combination with PEG promoter-regulated melanoma differentiation-associated gene-7 recombinant adenoassociated virus system (rAAV-PEG-MDA-7) on transplant tumor of hepatocellular carcinoma in mice with non-obese diabetic-severe combined immunodeficiency (NOD-SCID).Methods The rAAV-PEG-MDA-7 expression system and NOD-SCID mice subcutaneous transplant tumor models of HepG2,the hepatocellular carcinoma cell strain,were constructed.Mice in control group received rAAV-PEG empty vector injection via the tail vein and subcutaneous normal saline injection adjacent to the tumor.By contrast,mice in eight experimental groups were treated with tail injection of rAAV- PEG-MDA- 7 loaded with virus of various magnitudes and subcutaneous octreotide injection of different dosages adjacent to the tumor.The mice were sacrificed at day 21 for comparison of the mass of transplant tumors.Results Either rAAV-PEG-MDA-7 or octreotide alone could inhibit transplant tumor growth in mice.Octreotide of various dosages (5 μg/kg and 30 μ g/kg) in combination with low-dose MDA-7 (1 × 1011 particles) was associated with strengthened tumor inhibitory effect as compared with MDA-7 alone [ (1.14±0.24) g and (0.98±0.11) g vs (1.71±0.26) g,both P＜0.05].Such effect was also found in octreotide (5 μg/kg and 30 μg/kg) with high-dose MDA-7 (5×1011particles) as compared with MDA-7 alone [ (1.05±0.21) g and (0.90±0.18) g vs (1.41±0.20) g,both P＜0.05 ].By contrast,MDA-7 of various dosage ( 1 × 1011 particles and 5× 1011 particles) in combination with lowdose octreotide (5 μg/kg) conferred superior efficacy as compared with octreotide alone [ (1.14±0.24) g and (1.05±0.21) g vs (1.68±0.18) g,both P＜0.05].Additionally,MDA-7 of various dosage (1×1011 particles and 5 × 1011 particles) in combination with high-dose octreotide (30 μg/kg) was associated with increased tumor inhibitory effect as compared with octreotide alone [ (0.98±0.11 ) g and (0.90±0.18 ) g vs (1.34±0.12 )g,both P＜0.05].Conclusion The combination of MDA-7 and octreotide is associated with enhanced inhibitory effect on transplant tumor of hepatocellular carcinoma in mice. Key words: Octreotide; Melanomadifferentiation-associatedgene-7; Carcinoma, hepatocellular; Neoplasm transplantation