葡萄球菌肠毒素A脂质体对小鼠原位移植H22肝癌的治疗作用

Antitumor efficacy of staphylococcal enterotoxin A liposomes in vivo

目的 观察葡萄球菌肠毒素A(staphylococcalenterotoxinA ,SEA)脂质体对小鼠原位移植H2 2肝癌的治疗作用。方法 逆相蒸发法制备SEA脂质体 ,肝脏原位注射法建立小鼠H2 2原位肝癌模型 ,静脉注射SEA脂质体 ,观察瘤重及抑瘤率。并用ELISA法检测肝组织和血浆中细胞因子TNF α、IFN γ的水平 ;免疫组化染色法观察肿瘤组织TIL的浸润情况。结果 与游离SEA相比 ,SEA脂质体能显著增加肝癌组织TIL浸润和肝脏组织中TNF α、IFN γ水平 ,并对小鼠原位H2 2肝癌具有明显抑制作用 ,而游离SEA无此作用。SEA脂质体组血浆中细胞因子水平较游离SEA组显著降低。结论 SEA脂质体可以显著增加SEA治疗小鼠原位H2 2肝癌的疗效 ,并有可能降低由细胞因子介导的毒性作用。可能的机制是SEA脂质体具有肝靶向性 ,能激活肝癌原位TIL ,激活的TIL及其分泌的大量细胞因子参与了抗肿瘤。

Objective To investigate the therapeutic effects of staphylococcal enterotoxin A (SEA) liposomes on orthotopic transplanted H22 HCC in mice. Methods SEA liposomes were prepared by the method of reverse phase evaporation. The orthotopic liver cancer model was established in mice through local injection of H22 HCC cells into the liver of mice. Meanwhile, SEA liposomes were intravenously administered in the mice. In vivo antitumor efficacy of SEA liposomes was evaluated by the measurement of tumor weight. The TIL density and cytokine level in the liver and plasma were determined by immunohistochemical staining and ELISA, respectively. Results After intravenous administration of SEA liposomes, the antitumor activity of SEA liposomes was dramatically increased with enhanced TIL density and cytokine level in the liver associated with significant reduction of plasma cytokine level. Conclusions SEA liposomes have an enhanced antitumor efficacy. These advantages are probably due to their liver targeting characteristics and consequently a higher local TIL activation and a lower systemic cytokine level.