羧胺三唑联合小剂量地塞米松抗肿瘤作用研究

The anti-tumor effects of carboxyamidotriazole and low dose dexamethasone

目的研究羧胺三唑(CAI)对小鼠Lewis肺癌移植瘤生长的抑制作用及其作用机制。初步探索CAI与小剂量地塞米松(DEX)合用是否有抑瘤增效作用。方法建立C57BL/6小鼠Lewis肺癌移植瘤模型,评估CAI、DEX及其合用组的抗肿瘤疗效。ELISA法检测肿瘤匀浆中肿瘤坏死因子-α(TNF-α)水平。免疫荧光法对提取的肿瘤内巨噬细胞进行鉴定。RT-PCR法检测肿瘤内巨噬细胞中TNF-αmRNA表达水平。结果 CAI抑制移植瘤的生长。同时CAI能降低肿瘤内巨噬细胞中TNF-α的水平(P<0.01)。CAI与小剂量DEX联合应用,其抑瘤作用及抑制TNF-α水平与单用组相比明显增强(P<0.05)。结论 CAI能够抑制移植瘤生长,其作用机制可能与抑制肿瘤中巨噬细胞的TNF-α水平有关。通过与地塞米松联合应用,可起到抗肿瘤增效作用。

Objective To explore the effect of carboxyamidotriazole （CAI） on the Lewis lung carcimoma growth and its underlying mechanisms.Besides,this study proposes whether the combination of CAI and low dose dexamethesone（DEX）can enhance the anti-tumor effect.Methods A mouse model with transplanted tumor was established to evaluate the anti-cancer effects of the CAI,DEX and their combination.Tumor tissue samples were homogenized followed by ELISA to detect the level of tumor necrosis factor-α （TNF-α）.The macrophages extracted from tumor tissues were stained and indentified by F4/80 immuno-fluorescent test.TNF-α mRNA expression level was analyzed by RT-PCR.Results CAI could inhibit the growth of mouse transplanted tumor.CAI highly significantly downregulated TNF-α level within macrophages from tumor tissues（P ＜ 0.01）.The combination of CAI and DEX showed more significant inhibitory effect on the growth of transplanted tumor and downregulated TNF-α level than single drug respectively（P ＜0.05）.Conclusions CAI inhibits tumor growth may cause by suppressing TNF-α production in the macropbages from tumor tissues.As those actions of CAI could be enhanced by low dose DEX.