IL-12基因联合吡柔比星治疗裸鼠膀胱癌移植瘤的实验

目的 探讨联合应用白细胞介素12(IL-12)质粒和吡柔比星（THP）对人膀胱癌裸鼠移植瘤生长的抑制作用。方法 将人EJ膀胱癌细胞株裸鼠腋下接种，成瘤后设4组（每组6只）：联合组于骨骼肌注射IL-12真核表达质粒pcAGGS-mIL-12和腹腔注射THP;IL-12组骨骼肌注射pcAGGS-mIL-12;THP组腹腔注射THP;对照组肌肉及腹腔注射0.9%氯化钠溶液，以上注射每周2次，共4次。观察各组裸鼠肿瘤大小变化。4周后处死荷瘤鼠。免疫组织化学法检测肿瘤内VEGF 表达。ELISA法测定血液及肿瘤组织中IL-12和γ-干扰素(IFN-γ)的表达。结果 联合组肿瘤生长明显抑制，瘤重及体积明显小于其他组。ELISA法表明IL-12组和联合组 IL-12和IFN-γ都高表达。免疫组织化学法表明联合组VEGF基因表达量明显低于其他组（P<0.05）。结论 联合应用IL-12真核表达质粒pCAGGS-mIL-12和THP，对人膀胱癌裸鼠移植瘤的抑制作用明显强于单独应用IL-12和THP。

Experimental of Combining Therapy with IL-12 Gene and THP in Bladder Cancer Nude Mice Model

ObjectiveTo explore the inhibition of mouse interleukin-12 (IL-12) gene and THP on bladder cancer nude mice model.Methods After subcutaneous injection of EJ human bladder tumor cells to the nude mice subaxillary，Nude mice were divided into four groups randomly(Combine，IL-12，THP and control groups).Nude mice in Combine group were injected plasmid pCAGGS-mIL-12 on skeletal muscle and THP peritoneally.IL-12 group only were injected plasmid pCAGGS-mIL-12 on skeletal muscle； THP group were injected THP peritoneally； Control group were injected saline peritoneally and on skeletal muscle.All injections were carried two times per week for two weeks.The expression of IL-12 and IFN-γ in blood was assayed by an enzyme linked immunosorbent assay (ELISA)at one week after injection.Mice were sacrificed at fourth week.The level of VEGF in tumor tissue was detected by immunohistochemistry.IL-12 and IFN-γ in tumor tissue was assayed by ELISA. Results In combine group，tumor growth were retarded compared with the other groups.There was a significantly low expression of VEGF in the combined group； IL-12 and IFN-γ were increased in both the IL-12 group and combined group.Conclusion Both injected pCAGGS-mIL-12 on skeletal muscle and THP peritoneally could inhibit the xenograft in nude mice planted with human bladder tumor cells.