丙泊酚对肿瘤细胞肺转移及E钙粘蛋白、β-连环蛋白表达的影响

摘要

目的：探讨不同剂量丙泊酚对大鼠MADB106细胞肺转移和肿瘤组织中E钙粘蛋白（E-cadherin）、β-连环蛋白（β-catenin）的影响。方法 Fischer344雄性大鼠40只，随机分为4组（每组10只）：生理盐水组（S组）、脂肪乳剂组（F组）、丙泊酚30㎎/㎎组（P1组）和50 mg/kg组（P2组）。1%戊巴比妥钠50 mg/kg腹腔注射后行股静脉置管，分别泵入等容量的生理盐水、脂肪乳剂和丙泊酚，1 h后静注0.5 ml MADB106肿瘤细胞（2×105个）。3周后处死，计数肺表面转移瘤数目及转移抑制率；采用免疫组化法检测肿瘤组织中E-cadherin和β-catenin的表达，用IPP图像分析系统对结果进行半定量分析。结果 S组与F组肺转移瘤数目、转移抑制率和肿瘤组织中E-cadherin、β-catenin的表达均无显著差异（P>0.05）。与S组和F组相比，P1组和P2组的肺转移瘤数目减少（P<0.01），转移抑制率增加（P<0.01），E-cadherin和β-catenin蛋白的表达减少（P<0.05）；肺转移瘤数目及E-cadherin和β-catenin蛋白的表达与丙泊酚剂量负相关，Pearson相关系数分别为-0.879、-0.755、-0.693（P<0.01）。结论丙泊酚可通过抑制Wnt/β-catenin通路，下调转移瘤组织中E-cadherin和β-catenin的表达，从而抑制MADB106细胞肺转移，呈剂量依赖性。%Objective To investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats. Methods Forty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2 × 105) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry. Results Compared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01). Conclusion Propofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin andβ-catenin expressions in the metastatic tumor tissue.