MDM2分子成像评估乳腺癌化疗敏感性的实验研究

Research of MDM2 molecular imaging for the evaluation of chemotherapeutic response in breast cancer xenograft

目的:利用小鼠双微体扩增基因(Mouse double minute 2,MDM2)反义寡核苷酸(Antisense oligonucleotide,AS)合成影像分子探针,探讨MDM2分子成像评估乳腺癌化疗敏感性的可行性。方法:应用紫杉醇作用于MDM2表达程度不同的乳腺癌(MCF-7)细胞,MTT法检测紫杉醇对MCF-7细胞的抑制率,99Tcm标记MDM2反义寡核苷酸合成分子探针,两组MDM2表达程度不同的荷乳腺癌裸鼠分别进行MDM2分子成像,评估MDM2表达程度,两组荷瘤裸鼠分别进行紫杉醇化学药物治疗,不同时间点检测肿瘤体积,绘制肿瘤生长曲线。结果:MDM2表达程度不同的MCF-7细胞对紫杉醇反应不同,MDM2表达程度越高,紫杉醇抑瘤率越低,MDM2分子成像能够评估荷乳腺癌裸鼠的MDM2表达程度,紫杉醇对MDM2表达程度不同的荷乳腺癌裸鼠的抑瘤效果不同。结论:MDM2分子成像能够在荷乳腺癌裸鼠化疗前准确评价MDM2表达程度,预测荷乳腺癌裸鼠对紫杉醇化学药物治疗的敏感性。

Objective： To investigate the possibility of using MDM2 molecular imaging on evaluating chemotherapeutic response in breast cancer xenograftm, the molecular probe was synthesized using MDM2 antisense oligonucleotide（AS）. Methods： The MCF-7 cell of different MDM2 expression was transfected with paclitaxel. The inhibition efficiency of MCF-7 to paclitaxel was observed by MTr assay. MDM2 AS was radiolabeled with ^99Tc^m. The level of MDM2 expression was evaluated with molecular imaging in the breast cancer xenograft of different MDM2 expression. Two group xenografts of different MDM2 expression were treated with paclitaxel. The tumor volume was determined at different times and growth curve was drawn. Results： The MCF-7 cell of different MDM2 expression have various response to the paclitaxel. The tumor of higher MDM2 expression have lower response to paclitaxel. MDM2 molecular imaging can evaluate the MDM2 expression in breast cancer xenograft. The breast cancer xenograft of various MDM2 expression have different inhibition efficiency to paclitaxel. Conclusion： MDM2 molecular imaging can exactly evaluate the MDM2 expression prior to the chemotherapy and anticipate the sensitivity of the breast cancer xenograft to chemotherapy.