Naidu K A, Tang J L, Naidu K A, Prockop L D, Nicosia S V, Coppola D
Department of Neurology, H. Lee Moffitt Cancer Center and Research Institute, College of Medicine, University of South Florida, Tampa, USA.
J Neurooncol. 2001 Aug;54(1):15-22. doi: 10.1023/a:1012545311054.
Human glioblastomas (gliomas) are characterized as highly invasive and rapidly growing brain tumors. In this study, we present data on in vitro effect of ascorbyl stearate (Asc-S), a liphophilic derivative of ascorbic acid on cell proliferation, transformation, apoptosis and modulation of expression of insulin-like growth factor-I receptor (IGF-IR) in human glioblastoma multiforme (T98G) cells. Asc-S showed significant inhibition of fetal bovine serum and human recombinant insulin-like growth factor-I (IGF-I) dependent cell proliferation in a dose dependent manner. Treatment of T98G cells with 0, 50, 100 and 150 microM Asc-S for 24h slowed down the cell multiplication cycle with significant accumulation of cells at late S/G2-M phase of cycle. Asc-S treatment (100 microM) reversed the transformed phenotype as determined by clonogenecity in soft agar and also induced apoptosis of T98G. These changes were found to be associated with significant decrease in IGF-IR expression in dose and time dependent manner compared to untreated controls. The data clearly demonstrate that Asc-S has antiproliferative and apoptotic effect on T98G cells probably through modulation of IGF-IR expression and consequent facilitation of programmed cell death.
人类胶质母细胞瘤（胶质瘤）的特征是具有高度侵袭性且生长迅速的脑肿瘤。在本研究中，我们展示了抗坏血酸硬脂酸酯（Asc-S），一种抗坏血酸的亲脂性衍生物，对多形性胶质母细胞瘤（T98G）细胞的增殖、转化、凋亡以及胰岛素样生长因子-I受体（IGF-IR）表达调节的体外作用数据。Asc-S以剂量依赖性方式显著抑制胎牛血清和人重组胰岛素样生长因子-I（IGF-I）依赖性细胞增殖。用0、50、100和150微摩尔/升的Asc-S处理T98G细胞24小时，减缓了细胞增殖周期，细胞在周期的S/G2-M晚期阶段显著积累。Asc-S处理（1μM）可逆转由软琼脂克隆形成能力所确定的转化表型，并诱导T98G细胞凋亡。与未处理对照相比，发现这些变化与IGF-IR表达以剂量和时间依赖性方式显著降低有关。数据清楚地表明，Asc-S对T98G细胞具有抗增殖和凋亡作用，可能是通过调节IGF-IR表达并进而促进程序性细胞死亡。
