不同铂类联合紫杉类或长春瑞滨对非小细胞肺癌荷瘤裸鼠抑瘤作用的实验研究

Experimental study of different platinum alone or combined with taxanes or vinorelbine on nude mice implanted human non-small cell lung cancer NCI-H460 cells in vivo

目的探讨洛铂(LBP)、顺铂(DDP)和卡铂(Cab)单用或联合紫杉醇(PTX)、多西他赛(DOC)和长春瑞滨(NVB)对非小细胞肺癌(NSCLC)荷瘤裸鼠的抑瘤作用。方法选用人大细胞肺癌细胞株NCI-H460接种于裸小鼠皮下成瘤。单药抑瘤实验中设LBP(3.75、7.5、15 mg/kg)3组及Cab(60mg/kg)、DDP(5mg/kg)各1组;联合抑瘤实验设LBP(7.5mg/kg)、DPP(2.5mg/kg)分别与DOC(5mg/kg)、PTX(12mg/kg)、NVB(5mg/kg)联合共6组以及各自单药5组,每组均随机分配6只成瘤小鼠,经静脉d0、d7给药(PTX d0、d2、d4给药除外)。各设1组对照组,每组12只。每周2～3次记录瘤体体积和裸鼠体重,并计算相对肿瘤增殖率(T/C)。结果 (1)单药抑瘤实验中,LBP抑瘤效果与剂量相关,中、高剂量组的T/C分别为51.1%和36.3%,低于Cab组(51.6%),但LBP高剂量组有1只小鼠出现药物相关性死亡。对裸鼠体重的影响由大到小依次为:DDP组>LBP高剂量组>LBP中剂量组>Cab组>LBP低剂量组。(2)联合抑瘤实验中,LBP+PTX组的T/C最低,为24.4%,明显优于DDP+PTX组(P<0.05);LBP+DOC组和DDP+DOC组亦对小鼠体重有明显影响。结论 LBP单药对NCI-H460荷瘤小鼠的抑瘤作用呈剂量依赖性,介于DDP与Cab之间;而LBP联合PTX的抑瘤作用最强,明显优于DDP联合PTX及其他两药联合。

Objective To investigate the inhibitory effects of lobaplatin（LBP）,cisplatin（DDP） and caboplatin（Cab）alone or combined with paclitaxel（PTX）,docetaxel（DOC）and vinorelbine（NVB）respectively against nude mice bearing human non-small cell lung cancer（NSCLC） NCI-H460 cells in vivo. MethodsNCI-H460 cells were implanted into nude mice.In monotherapy treatment study,the nude mice bearing human NSCLC NCI-H460 cells were randomly divided into 5 groups with 6 mice in each group.In concomitant treatment study,the nude mice bearing human NSCLC NCI-H460 cells were randomly divided into 11 groups,and each group had 6 mice.The volume of tumor,the weight of nude mice and tumor volume were respectively measured and calculated 2-3 times per week. ResultsMonotherapy treatment study showed that anti-tumor effect of LBP was typically dose-related.T/C of median dose group and high dose group were 51.1% and 36.3%,which was higher than Cab group.There was drug-related death in LBP high dose group.The change of nude body weigh was in the following pattern： DDP groupLBP high dose groupLBP median dose groupCab groupLBP low dose group.The concomitant treatment study showed that T/C of LBP＋PTX group（24.4%） was the lowest of all combination.LBP＋DOC group,DDP＋DOC group obviously influenced on body weight. ConclusionFor nude mice implanted NCI-H46 cells,the anti-lung cancer effect of LBP is dependent on dose between the effect of DDP and Cab.The synergy effect of LBP combined with PTX is strongest,much better than DDP plus PTX.