Non-small cell lung carcinoma therapy using mTOR-siRNA.
Non-small cell lung carcinoma therapy using mTOR-siRNA.
复制标题
DOI：
--
复制
发表时间：
2012
影响因子：
1.4
通讯作者：
H. Matsubara;K. Sakakibara;T. Kunimitsu;Hiroyasu Matsuoka;Kaori Kato;N. Oyachi;Y. Dobashi;M. Matsumoto
中科院分区：
文献类型：
--
作者：
H. Matsubara;K. Sakakibara;T. Kunimitsu;Hiroyasu Matsuoka;Kaori Kato;N. Oyachi;Y. Dobashi;M. Matsumoto
分子靶向药物在非小细胞肺癌(NSCLC)治疗中发挥着重要作用。已发表的研究已经调查了被归类为分子靶向剂的新药，这些药物可以抑制雷帕霉素的哺乳动物靶标(MTOR)。我们专注于一种小干扰RNA(SiRNA)，它能特异性地抑制mTOR，并且副作用较少。为了评价siRNA的抗肿瘤作用，对细胞的增殖、凋亡和迁移进行了检测。将siRNA导入非小细胞肺癌细胞。计数培养6天后细胞的数量，以确定细胞增殖的变化。通过吸收光谱仪检测胞浆中DNA-组蛋白复合体来评价细胞的凋亡水平。通过使用商业趋化分析试剂盒计算通过特定过滤器的细胞数量来评估迁移的变化。MTOR-siRNA可抑制细胞增殖，与对照组相比，细胞数减少37.3%(p=0.034)。对非小细胞肺癌细胞的凋亡率分析显示，mTOR-siRNA转染后细胞的凋亡率增加了16.7%(p=0.016)，并且mTOR-siRNA显著抑制了细胞的迁移(p=0.0001)。我们证实了mTOR-siRNA在体外可以诱导NSCLC细胞的凋亡并抑制其增殖和迁移。使用mTOR-siRNA的进一步研究可能有助于开发一种替代疗法，最大限度地发挥mTOR抑制的抗肿瘤作用。
Molecular targeting agents play important roles in non-small-cell lung cancer (NSCLC) therapy. Published studies have investigated new drugs categorized as molecular targeting agents that inhibit the mammalian target of rapamycin (mTOR). We focused on a small interfering RNA (siRNA) that specifically inhibits mTOR and has fewer side effects. To evaluate the antitumor effects of the siRNA, cell proliferation, apoptosis, and migration were assessed. In the study group, the siRNA was transfected into NSCLC cells. The number of cells present after 6 days of culture was counted to determine changes in cell proliferation. The level of apoptosis was evaluated by the detection of DNA-histone complexes in the cytoplasmic fraction using an absorption spectrometer. Changes in migration were evaluated by calculating the number of cells that passed through a specific filter using a commercial chemotaxis assay kit. mTOR-siRNA transfection inhibited cell proliferation as indicated by 37.3% (p = 0.034) decrease in the number of cells compared with the control cells. Analysis of the level of apoptosis in NSCLC cells revealed 16.7% (p = 0.016) increase following mTOR-siRNA transfection, and mTOR-siRNA transfection significantly inhibited cell migration by 39.2% (p = 0.0001). We confirmed that mTOR-siRNA induces apoptosis and inhibits the proliferation and migration of NSCLC cells in vitro. Further studies using mTOR-siRNA may aid in the development of an alternative therapy that maximizes the antineoplastic effect of mTOR inhibition.