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

发布时间：2018-03-05 04:01

本文选题：卵巢肿瘤　切入点：抗肿瘤联合化疗方案　出处：《肿瘤》2015年01期 　论文类型：期刊论文

【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(P0.05),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(P0.05)。MTD组裸鼠白细胞的数量较对照组及LDM组均明显降低(P0.05)。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。
[Abstract]:Objective: to observe the effects of maximum tolerated dose chemotherapy (MTD) and low-dose low-dose metronomic chemotherapy (LDMs) on the growth of human ovarian cancer bearing nude mice and their transplanted tumors. To investigate the effects of breast cancer resistant protein (BCRP), lung resistance protein (LRP) and tumor stem cell marker CD133 (CD133) on the expression of breast cancer resistant cancer resistant protein in nude mice bearing human ovarian cancer. Methods: human ovarian cancer cell line SKOV3 was used to establish subcutaneous transplanted tumor model of human ovarian carcinoma in nude mice. Type. 36 nude mice were randomly divided into 3 groups (12 rats in each group: control group, MTD group and LDM group. The expression levels of BCRPP-LRP and CD133 protein were detected by Western blotting. Hematoxylin-eosin HEHE staining was used to detect the micrometastases and histomorphologic changes in the viscera of nude mice. The volume of transplanted tumor in LDM group and LDM group was significantly smaller than that in MTD group. MTD group and LDM group were 27.00% and 54.29.MTD group and LDM group respectively were lower than control group P0.05. MTD group. MTD group. MTD group was lower than control group. MTD group. MTD group was lower than control group P0.05. MTD group. MTD group was lower than control group P0.05. MTD group. MTD group was lower than control group P0.05. MTD group. The number of leukocytes in nude mice was significantly lower than that in control group and LDM group. There were two nude mice with hepatocyte fatty degeneration. MTD and LDM group, the expression levels of BCRPnLRP and CD133 protein were significantly higher than that of control group (P 0.05), but the expression of CD133 protein in LDM group was significantly higher than that in control group (P 0.05). The expression level of BCRP protein and CD133 protein was significantly lower than that in MTD group. Conclusion: under the same cumulative drug dosage, the inhibitory effect of BCRP on the growth of subcutaneous transplanted tumor of SKOV3 cells bearing human ovarian cancer is better than that of MTD. Compared with the treatment mode of LDM, the residual tumor cells with some characteristics of tumor stem cells and high expression of drug-resistance associated protein are easy to be enriched. A potential therapeutic modality that can reduce tumor recurrence and increase chemosensitivity.
【作者单位】：解放军白求恩国际和平医院妇产科;石家庄市第四医院妇产科;
【分类号】：R737.31

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