树突状细胞对小剂量化疗疗效影响的基础研究

目的 研究树突状细胞对小剂量化疗疗效的影响,探讨小剂量化疗的可能机制.方法 以615小鼠的前胃癌细胞株(MFC)造模,在体外用rmGM-CSF和rmIL-4从荷瘤小鼠骨髓细胞分化、诱导未成熟树突状细胞.分为4组:小剂量化疗组、树突状细胞组、小剂量化疗+树突状细胞组、对照组,以BAX试剂盒检测肿瘤凋亡情况.在瘤体内注射树突状细胞,计算抑瘤率、特异性细胞毒性T淋巴细胞(CTL)的增殖及其对肿瘤细胞的特异性杀伤作用.结果 小剂量化疗能诱导肿瘤细胞凋亡,BAX 基因产物表达增多.注射侧抑瘤率小剂量化疗+DC组、小剂量化疗组、DC组分别为100%、67.22%和57.98%.对侧抑瘤率小剂量化疗+DC组、小剂量化疗组、DC组分别为87.58%、59.69%和48.24%.体内凋亡肿瘤细胞致敏的DC能显著刺激T淋巴细胞增殖,其诱导的CTL对MFC有显著的杀伤作用,在效靶比为40∶ 1、20∶ 1、10∶ 1和5∶ 1时72 h杀伤率分别为87.64%、70.32%、34.63%和13.87%.并能特异性杀伤小鼠前胃癌细胞MFC(P<0.01).结论 小剂量化疗的机制与肿瘤细胞凋亡及免疫促进有一定的相关.

A fundamental research on DCs for their role in low dose chemotherapy

Objective To investigate the value of dendritic cells in immunotherapy and their role in low dose chemotherapy (5-Fu, DDP).Method MFC was injected into 615 mice to get tumor models, and immature DCs were induced from bone marrow in vitro by rmGM-CSF and rmIL-4. All animals were divided into 4 groups: low dose chemotherapy group, DC group, low dose chemotherapy+DC group and control group. Apoptosis of tumor cells was detected by using LASB. The inhibition ratio of proliferation of MFCs, the proliferation of CTLs and its specific lethal effect on tumor cells were analysed.Result Low dose chemotherapy induced apoptosis of tumor cells. Inhibition ratio of proliferation of MFC of injected side were 100%, 67.22%, 57.98% respectively in both low dose chemotherapy and DC, low dose chemotherapy alone and DC alone. The inhibition ratio of proliferation of MFCs on injected side were 87.58% (low dose chemotherapy+DC group), 59.69% (low dose chemotherapy group) and 48.24% (DC group) respectively. The DCs also increased proliferation and activation of CTLs, which reinforced the lethal effect on MFCs (P<0.01). When the effector-to-target ratio was 40:1,20:1,10:1 and 5:1,the kill rate after 72h averaged 87.64%,70.32%, 34.63% and 13.87% respectively.Conclusion The mechanisms of low dose chemotherapy are correlated to apoptosis of tumor cells and immunologic enhancement.