Department of Pathology, Hainan Medical College, Haikou, Hainan 571101, P.R. China.
Mol Med Rep. 2013 Jun;7(6):1912-8. doi: 10.3892/mmr.2013.1434. Epub 2013 Apr 18.
Malignant gliomas persist as a major disease responsible for high morbidity and mortality rates in adults. Differentiation therapy has emerged as a promising treatment modality. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene function is commonly lost in primary gliomas, particularly in glioblastomas, and this is associated with tumor differentiation. PTEN gene deletion is one of the main molecular events in gliomas. In this study, we aimed to explore the effect and mechanisms of PTEN on cholera toxin (CT)‑induced SWO-38 glioma cell differentiation. It has been shown that transfection of the exogenous PTEN gene induces glioma cell differentiation; however, the underlying mechanism remains to be elucidated. Results of the present study showed that CT-induced SWO-38 glioma cell differentiation was characterized by morphological changes, the increased expression of glial fibrillary acidic protein (GFAP), an accumulation of cells in the G0/G1 phase of the cell cycle, the decreased expression of cyclin D1 and a decreased invasion and migration capacity. Silencing of the PTEN protein using RNA interference resulted in suppressed cell differentiation. Furthermore, inhibition of the PI3K/AKT pathway by the inhibitor LY294002 led to attenuated differentiation, while differentiation remained stable with the inhibition of the MAPK/ERK pathway by PD0325901. Thus, PTEN may be important in glioma cell differentiation.
恶性神经胶质瘤仍然是导致成年人高发病率和死亡率的主要疾病。分化治疗已成为一种有前途的治疗方式。磷酸酶和张力蛋白同源物缺失于第 10 号染色体(PTEN)基因功能在原发性神经胶质瘤中通常丧失,特别是在神经胶质瘤中,这与肿瘤分化有关。PTEN 基因缺失是神经胶质瘤的主要分子事件之一。在这项研究中,我们旨在探讨 PTEN 对霍乱毒素(CT)诱导的 SWO-38 神经胶质瘤细胞分化的影响及其机制。已经表明,转染外源性 PTEN 基因可诱导神经胶质瘤细胞分化;然而,其潜在机制仍有待阐明。本研究结果表明,CT 诱导的 SWO-38 神经胶质瘤细胞分化的特征是形态变化、神经胶质纤维酸性蛋白(GFAP)的表达增加、细胞周期的 G0/G1 期细胞积累、周期蛋白 D1 的表达减少以及侵袭和迁移能力降低。使用 RNA 干扰沉默 PTEN 蛋白可抑制细胞分化。此外,PI3K/AKT 通路抑制剂 LY294002 导致分化减弱,而 MAPK/ERK 通路抑制剂 PD0325901 使分化稳定。因此,PTEN 可能在神经胶质瘤细胞分化中起重要作用。