目的 观察不同剂量的奥曲肽联合PEG启动子调控的黑色素瘤分化相关基因7表达重组腺相关病毒系统(rAAV-PEG-MDA-7)对非肥胖糖尿病-重症联合免疫缺陷(NOD-SCID)小鼠肝癌移植瘤的抑制作用.方法 构建rAAV-PEG-MDA-7表达系统并建立肝癌细胞株HepG2的NOD-SCID小鼠皮下移植瘤模型,以尾静脉注射rAAV-PEG空载体+肿瘤周边皮下注射生理盐水为对照,按照尾静脉注分射不同病毒量的rAAV-PEG-MDA-7及肿瘤周边皮下注射不同剂量的奥曲肽组合为8个实验组.注射药物后21d处死小鼠,比较各组小鼠移植瘤质量.结果 单独应用rAAV-PEG-MDA-7或奥曲肽均能抑制小鼠移植瘤的生长.不同剂量的奥曲肽(5μg/kg、30 μg/kg)与低剂量MDA-7(1×1011 particles)联用时,可以增加MDA-7的抑制肿瘤作用[(1.14±0.24)g,(0.98±0.11)g比(1.71±0.26)g,均P<0.05];不同剂量奥曲肽(5 μg/kg、30 μg/kg)与高剂量MDA-7(5×1011 particles)联用时,亦可增加MDA-7的抑制肿瘤作用[(1.05±0.21)g、(0.90±0.18)g比(1.41±0.20)g,均P<O.05].不同剂量MDA-7(1×1011 particles、5×1011particles)与低剂量奥曲肽(5μg/kg)联用时,可以增加奥曲肽的抑制肿瘤作用[(1.14±0.24)g、(1.05±0.21)g比(1.68±0.18)g,均P<0.05];不同剂量MDA-7(1×1011 particles、5×1011particles)与高剂量奥曲肽(30 μg/kg)联用时,亦可增加奥曲肽的抑制肿瘤作用[(0.98±0.11)g、(0.90±0.18)g比(1.34±0.12)g,均P<O.05].结论 MDA-7与奥曲肽联合应用可以增强对小鼠肝癌移植瘤的抑制作用.
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.