Tezcan Gulcin, Tunca Berrin, Bekar Ahmet, Yalcin Murat, Sahin Saliha, Budak Ferah, Cecener Gulsah, Egeli Unal, Demir Cevdet, Guvenc Gokcen, Yilmaz Gozde, Erkan Leman Gizem, Malyer Hulusi, Taskapilioglu Mevlut Ozgur, Evrensel Turkkan, Bilir Ayhan
Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
Cell Mol Neurobiol. 2015 Mar;35(2):175-87. doi: 10.1007/s10571-014-0109-y. Epub 2014 Sep 12.
Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract.
多形性胶质母细胞瘤(GBM)是最致命的人类恶性肿瘤之一。GBM的治愈方法仍然难以捉摸,总体生存时间不到1年。因此,需要开发更有效的治疗方法来治疗这些患者。某些源自草药和食用植物的植物化学物质诱导肿瘤细胞死亡已成为癌症治疗研究的一个新前沿。尽管已在几种癌症类型中确定了无花果(Ficus carica)乳胶(FCL)的抗癌作用,但尚未研究这种乳胶对GBM肿瘤的作用。因此,在本研究中,使用WST-1测定法在T98G、U-138 MG和U-87 MG GBM细胞系中测试了FCL的抗增殖活性以及FCL-替莫唑胺(TMZ)组合的作用。使用膜联蛋白-V/FITC和TUNEL测定法分析细胞死亡机制,并使用鸡胚绒毛尿囊膜测定法测试FCL对侵袭的作用。为了确定FCL对GBM进展的影响,使用RT-qPCR分析了T98G细胞中40种与GBM相关的miRNA的表达水平。根据获得的数据,FCL导致对TMZ有不同反应的GBM细胞死亡,并且与TMZ联合使用时这种作用协同增强。此外,本研究首次证明了FCL对let-7d表达调节的作用,这可能是该提取物抗侵袭作用的重要潜在机制。