The effect of PTEN on proliferation and drug-, and radiosensitivity in malignant glioma cells.

The effect of PTEN on proliferation and drug-, and radiosensitivity in malignant glioma cells.
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发表时间:
2011-05
影响因子:
2
通讯作者:
N. Inaba;M. Kimura;K. Fujioka;K. Ikeda;Hiroko Somura;K. Akiyoshi;Yuriko Inoue;Mayumi Nomura;Yuji Saito;H. Saito;Y. Manome
N. Inaba;M. Kimura;K. Fujioka;K. Ikeda;Hiroko Somura;K. Akiyoshi;Yuriko Inoue;Mayumi Nomura;Yuji Saito;H. Saito;Y. Manome
中科院分区:
医学4区
文献类型:
--
作者:
N. Inaba;M. Kimura;K. Fujioka;K. Ikeda;Hiroko Somura;K. Akiyoshi;Yuriko Inoue;Mayumi Nomura;Yuji Saito;H. Saito;Y. Manome

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背景磷酸酶和张力蛋白同源物(PTEN)的缺失或突变经常在恶性胶质瘤中观察到,并负责疾病的进展。由于该分子是一个有前途的基因治疗的目标,与抗肿瘤剂,替莫唑胺,和电离辐射的组合,对神经胶质瘤增殖的影响进行了研究。材料和方法使用编码PTEN的腺病毒载体。感染后,增殖,细胞周期,以及药物和放射敏感性的变化进行了研究。结果PTEN的表达使细胞倍增时间延长1.21倍。它减少了G(1),增加了G(2)/M群体。强制性PTEN表达赋予替莫唑胺和/或电离辐射的敏感性。结论PTEN的表达在抑制胶质瘤细胞增殖的同时,还具有提高胶质瘤细胞化疗和放疗敏感性的作用。用于上调PTEN的方法可能在增加当前辅助疗法的功效中起作用。
BACKGROUND Deletions or mutations of the phosphatase and tensin homolog (PTEN) are frequently observed in malignant glioma and are responsible for progression of the disease. Since the molecule is a promising target for gene therapy, the effects of PTEN on glioma proliferation in combination with the anti-neoplastic agent, temozolomide, and ionizing radiation were investigated. MATERIALS AND METHODS An adenoviral vector encoding PTEN was used. After infection, changes in proliferation, the cell cycle, as well as drug- and radiosensitivity were investigated. RESULTS Expression of PTEN led to a 1.21-fold prolongation of the doubling time of the cells. It reduced G(1) and increased G(2)/M populations. Forced PTEN expression conferred sensitivity to temozolomide and/or ionizing radiation. CONCLUSION In addition to counteracting cell proliferation, expression of PTEN presented advantages in the chemo- and radiosensitivity of glioma cells. Methods for up-regulation of PTEN may have a role in increasing the efficacy of current adjuvant therapies.