The effect of silibinin in enhancing toxicity of temozolomide and etoposide in p53 and PTEN-mutated resistant glioma cell lines.
The effect of silibinin in enhancing toxicity of temozolomide and etoposide in p53 and PTEN-mutated resistant glioma cell lines.
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发表时间：
2015-03
影响因子：
2
通讯作者：
Rashid I. Elhag;E. Mazzio;K. Soliman
中科院分区：
文献类型：
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作者：
Rashid I. Elhag;E. Mazzio;K. Soliman
多形性胶质母细胞瘤（GBM）是一种顽固性脑肿瘤，预后差，生存率低。尽管预后不佳，但手术、放疗和替莫唑胺等联合治疗被认为是克服这种侵袭性癌症的标准方法。有必要确定可能增强替莫唑胺等标准药物化疗效果的潜在药物。在这个项目中，我们评估了水飞蓟素（水飞蓟籽的天然植物成分）对化疗药物如替莫唑胺、依托泊苷和伊立替康对LN229、U87和A172 （P53和磷酸酶和紧张素同源物(PTEN) -肿瘤抑制突变）胶质瘤细胞系的毒性作用。水飞蓟宾可增强替莫唑胺对LN229、U87和A172细胞的细胞毒作用。虽然水飞蓟宾仅在LN229细胞中降低了survivin蛋白的表达，但其增强化疗药物细胞毒性的能力与survivin蛋白水平无关。水飞蓟宾还能增强依托泊苷对LN229细胞的作用，而伊立替康则不能。未来的研究将需要评估水飞蓟宾的体内功效，以描述其作用机制和穿越血脑屏障的能力。
Glioblastoma multiforme (GBM) is an intractable brain tumor, associated with poor prognosis and low survival rate. Combination therapy such as surgery, radiotherapy and temozolomide is considered standard in overcoming this aggressive cancer, despite poor prognosis. There is a need to identify potential agents, which may augment the chemotherapeutic effects of standard drugs such as temozolomide. In this project, we evaluated the effects of silibinin, a natural plant component of milk thistle seeds, to potentiate toxic effects of chemotherapy drugs such as temozolomide, etoposide and irinotecan on LN229, U87 and A172 (P53 and phosphatase and tensin homolog (PTEN) -tumor suppressor-mutated) glioma cell lines. Data from this work suggest that silibinin was effective in potentiating the cytotoxic efficacy of temozolomide in LN229, U87 and A172 cells. While silibinin reduced survivin protein expression only in LN229 cells, its ability to potentiate cytotoxicity of chemo therapy drugs occurred irrespective of survivin protein levels. The data also demonstrated that silibinin potentiated the effect of etoposide and but not irinotecan in LN229 cells. Future research will be required to evaluate the in vivo efficacy of silibinin to delineate its mechanism of action and its ability to cross the blood-brain barrier.