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目的探讨β-葡萄糖神经酰胺(β-GC)联合乙型肝炎表面抗原(HBsAg)基因修饰树突状细胞(dendritic cell,DC)瘤苗治疗肝癌的作用。方法以重组腺病毒为载体构建HBsAg-DC瘤苗。将C57BL/6J小鼠随机分为6组(A-F,6只/组),其中A、B、C组接种PBS液2次,D、E、F组接种HBsAg-DC瘤苗2次。皮下注入HepG222.1.5肝癌细胞当天始,B、E组接受β-GC(1.5μg)腹腔注射,C、F组接受β-GC(15μg)灌胃给药,A、D组为安慰剂对照,比较不同组间移植瘤生长情况。结果 B、C组移植瘤生长较之A组明显受抑(P<0.05),E、F组移植瘤生长较之D组明显受抑(P<0.05)。A-F组移植瘤大小(mm3)分别为364.2±3.06,236.5±8.96,251.0±5.76,75.0±5.9,35.3±4.46,38.5±5.47。经腹腔注射给药与灌胃给药相比在抗瘤作用方面差异无统计学意义。结论β-GC经腹腔或灌胃给药均具有提高HBsAg-DC瘤苗的免疫治疗作用,其协同抗肿瘤效应的机制可能通过激活NKT细胞。
Objective To investigate the effect of β-glucosylceramide (β-GC) combined with dendritic cell (DC) modified hepatitis B surface antigen (HBsAg) gene therapy on hepatocellular carcinoma. Methods Recombinant adenovirus vector was used to construct HBsAg-DC vaccine. C57BL / 6J mice were randomly divided into 6 groups (A-F, 6 / group). Groups A, B and C were inoculated twice with PBS, and groups D, E and F were vaccinated twice with HBsAg-DC. Subcutaneously injected HepG222.1.5 hepatocarcinoma cells, group B and E received intraperitoneal injection of β-GC (1.5 μg) intraperitoneally, and groups C and F received intragastric administration of β-GC (15 μg). Groups A and D received placebo, Compare the growth of xenografts in different groups. Results The growth of transplanted tumors in groups B and C was significantly inhibited compared with that in group A (P <0.05). The growth of transplanted tumors in groups E and F was significantly inhibited compared with that in group D (P <0.05). The size of tumor xenografts in group A-F were 364.2 ± 3.06, 236.5 ± 8.96, 251.0 ± 5.76, 75.0 ± 5.9, 35.3 ± 4.46, 38.5 ± 5.47, respectively. There was no significant difference in anti-tumor effect between intraperitoneal injection and intragastric administration. Conclusion The intraperitoneal or intragastric administration of β-GC can improve the immunotherapeutic effect of HBsAg-DC vaccine, and its synergistic anti-tumor effect may be through activation of NKT cells.