MDM2 Molecular Imaging for the Prediction of Chemotherapeutic Sensitivity in Human Breast Cancer Xenograft
MDM2 Molecular Imaging for the Prediction of Chemotherapeutic Sensitivity in Human Breast Cancer Xenograft
复制标题
MDM2 分子成像预测人乳腺癌异种移植物的化疗敏感性
DOI：
10.2310/7290.2014.00018
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发表时间：
2014-08-01
影响因子：
2.8
通讯作者：
Zhao, Changjiu
中科院分区：
文献类型：
--
作者：
Fu, Peng;Sun, Li;Zhao, Changjiu
本研究的目的是探讨小鼠双分钟2(MDM2)分子成像技术预测乳腺癌异种移植瘤(BCX)化疗敏感性的可能性。将MDM2反义寡核苷酸(ASON)导入MCF-7细胞，用Western blotting检测MDM2的表达水平。3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑(3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑(4，5-二甲基四氮唑-2-基)-2，5-二苯基四氮唑(4，5-二甲基四氮唑-2-基)-2，5-二苯基四氮唑(4，5-二苯基四氮唑)比色法检测反义寡核苷酸和紫杉醇对MCF-7细胞的作用。通过注射ASON在裸鼠体内建立BCX，紫杉醇治疗后测量肿瘤体积。用99mTc标记MDM2反义寡核苷酸，制备MDM2分子探针，通过显像法和Western blotting检测MDM2的表达水平。MDM2 ASON以剂量依赖方式下调MDM2的表达，增加紫杉醇诱导的细胞生长抑制率。肿瘤影像显示肿瘤与骨骼肌(T/M)的比率在组间有显著差异。肿瘤MDM2蛋白表达与T/M比值在4小时(R=.880)和10小时(R=.886)相关。紫杉醇对荷瘤裸鼠的作用不同，不同浓度的反义寡核苷酸对肿瘤生长的影响也不同。MDM2分子成像是预测BCXs化疗敏感性的一种有前景的方法。
The aim of the present study was to investigate the possible use of mouse double-minute 2 (MDM2) molecular imaging to predict chemotherapeutic sensitivity in breast cancer xenografts (BCXs). MCF-7 cells were transfected with MDM2 antisense oligonucleotides (ASONs), and MDM2 expression levels were determined by Western blotting. Cell viability was assessed by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in MCF-7 cells transfected with ASONs and treated with paclitaxel. BCXs were established in nude mice by injection of ASONs, and tumor volumes were measured after paclitaxel treatment. MDM2 ASONs were labeled with 99mTc to generate an MDM2 molecular probe, and MDM2 expression levels were evaluated by imaging and Western blotting. MDM2 ASONs downregulated MDM2 expression in a dose-dependent manner and increased the rate of paclitaxel-induced cell growth inhibition. Imaging of tumors revealed significant differences in the tumor to skeletal muscle (T/M) ratio between groups. Tumor MDM2 protein expression was correlated with T/M ratios at 4 hours (R = .880) and 10 hours (R = .886). The effect of paclitaxel varied among nude mice bearing BCXs with different concentrations of ASONs, as shown by differences in tumor growth. MDM2 molecular imaging could be a promising method for predicting the sensitivity of BCXs to chemotherapy.