顺铂低剂量节拍化疗对荷人卵巢癌裸鼠及其移植瘤生长的影响  

Effect of low-dose metronomic chemotherapy with cisplatin on nude mice bearing human epithelial ovarian cancer and the xenograft tumors

作　　者：吴小华 张彩虹[1] 曹琴英[2] 孙亚楠[1] 周楠[1] 

机构地区：[1]解放军白求恩国际和平医院妇产科,河北石家庄050082 [2]石家庄市第四医院妇产科,河北石家庄050011

出　　处：《肿瘤》2015年第1期31-37,共7页Tumor

摘　　要：目的:观察采用顺铂(cisplatin,DDP)最大可耐受剂量化疗(maximum tolerated dose chemotherapy,MTD)和低剂量节拍化疗(low-dose metronomic chemotherapy,LDM)对荷人卵巢癌裸鼠及其移植瘤生长的影响,并探讨其对乳腺癌耐药蛋白(breast cancer resistant protein,BCRP)、肺耐药蛋白(lung resistance protein,LRP)和肿瘤干细胞标志物CD133表达水平的影响。方法:采用人卵巢癌细胞株SKOV3建立荷人卵巢癌裸鼠皮下移植瘤模型。36只裸鼠随机分为3组(每组12只):对照组、MTD组和LDM组。化疗期间观察裸鼠的一般情况和肿瘤生长状况,并计算抑瘤率。蛋白质印迹法检测各组移植瘤组织中BCRP、LRP和CD133蛋白的表达水平。苏木精-伊红(hematoxylin-eosin,HE)染色法观察裸鼠内脏有无微小转移病灶及组织形态学的改变。结果:MTD组和LDM组移植瘤的体积均小于对照组(P<0.05),且LDM组移植瘤的体积明显小于MTD组。MTD组和LDM组的抑瘤率分别为27.00%和54.29%。MTD组和LDM组裸鼠的体质量及进食量均低于对照组(P<0.05)。MTD组裸鼠白细胞的数量较对照组及LDM组均明显降低(P<0.05)。MTD组中有2只裸鼠出现肝细胞脂肪样变性。MTD和LDM组移植瘤中BCRP、LRP及CD133蛋白的表达水平均明显高于对照组(P均<0.05),但LDM组中BCRP蛋白和CD133蛋白的表达水平明显低于MTD组。结论:在累计药物剂量相同的情况下,LDM治疗模式对荷人卵巢癌SKOV3细胞裸鼠皮下移植瘤生长的抑制效果比MTD更好,而骨髓抑制等不良反应更轻。与LDM治疗模式相比,MTD治疗后残余的肿瘤病灶中具有部分肿瘤干细胞特性且耐药相关蛋白高表达的肿瘤细胞易被富集。因此,LDM是一种可以降低肿瘤复发并提高化疗敏感性的有潜力的治疗模式。Objective：To investigate the impact of low-dose metronomic chemotherapy（LDM） and maximum tolerated dose chemotherapy（MTD） with cisplatin on BALB/c nude mice bearing human ovarian cancer and the xenograft tumors of SKOV3 cells,and to explore the influence of these two chemotherapeutic protocols on expression levels of breast cancer resistant protein（BCRP）,lung resistance protein（LRP） and tumor stem cell marker CD1 33.Methods：The human ovarian cancer SKOV3 cells were used to establish BALB/c nude mice model bearing subcutaneous tumor xenografts.Thirty-six mice were randomly divided into three groups：control group（n = 12）,LDM group（n = 12） and MTD group（n = 12）.The general situation of nude mice and the growth of tumor xenografts were observed during chemotherapy,and the tumor inhibition rate was calculated.The expression levels of BCRP,LRP and CD1 33 proteins in tumor xenografts in nude mice were detected by Western blotting.The small metastatic lesions in internal organs and the pathological feature of tumor xenografts were observed by hematoxylin-eosin（HE） staining.Results：The volume of tumor xenografts of MTD and LDM groups were significantly smaller than that of the control group（P〈0.05）,while the tumor volume of LDM group was significantly smaller than that of MTD group.The tumor inhibition rates of MTD group and LDM group were 27.00%and 54.29%,respectively.The body weight and food-intake of mice in MTD group and LDM group were both significantly lower than those in the control group（all P〈0.05）.As compared to LDM group and the control group,white blood cell（WBC） count in MTD group was lower（P〈0.05）.Hepatocellular fatty degeneration was observed in two mice in MTD group.The expression levels of BCRP,LRP and CD1 33 proteins in tumor xenografts in MTD group and LDM group were significantly higher than those in the control group（all P〈0.05）,while the BCRP and CD1 33 protein expression levels in LDM group were lower than those in MTD group.Conclus

关 键 词：卵巢肿瘤 抗肿瘤联合化疗方案 多药耐药相关蛋白质类 肿瘤干细胞 

分 类 号：R737.31[医药卫生—肿瘤]