Glioblastoma multiforme (GBM) is the most aggressive type of glioma, displaying atypical glycosylation pattern that may modulate signaling pathways involved in tumorigenesis. Lectins are glycan binding proteins with antitumor properties. The present study was designed to evaluate the antitumor capacity of the Dioclea reflexa lectin (DrfL) on glioma cell cultures. Our results demonstrated that DrfL induced morphological changes and cytotoxic effects in glioma cell cultures of C6, U-87MG and GBM1 cell lines. The action of DrfL was dependent upon interaction with glycans, and required a carbohydrate recognition domain (CRD), and the cytotoxic effect was apparently selective for tumor cells, not altering viability and morphology of primary astrocytes. DrfL inhibited tumor cell migration, adhesion, proliferation and survival, and these effects were accompanied by activation of p38^MAPK and JNK (p46/54), along with inhibition of Akt and ERK1/2. DrfL also upregulated pro-apoptotic (BNIP3 and PUMA) and autophagic proteins (Atg5 and LC3 cleavage) in GBM cells. Noteworthy, inhibition of autophagy and caspase-8 were both able to attenuate cell death in GBM cells treated with DrfL. Our results indicate that DrfL cytotoxicity against GBM involves modulation of cell pathways, including MAPKs and Akt, which are associated with autophagy and caspase-8 dependent cell death.

多形性胶质母细胞瘤 (GBM) 是最具侵袭性的胶质瘤类型，显示出非典型糖基化模式，可能调节参与肿瘤发生的信号通路。凝集素是具有抗肿瘤特性的聚糖结合蛋白。本研究旨在评估Dioclea reflexa的抗肿瘤能力胶质瘤细胞培养物上的凝集素 (DrfL)。我们的结果表明，DrfL 在 C6、U-87MG 和 GBM1 细胞系的神经胶质瘤细胞培养物中诱导形态学变化和细胞毒性作用。DrfL 的作用取决于与聚糖的相互作用，并且需要碳水化合物识别域 (CRD)，并且细胞毒性作用显然对肿瘤细胞具有选择性，不会改变原代星形胶质细胞的活力和形态。DrfL抑制肿瘤细胞迁移、粘附、增殖和存活，这些作用伴随着p38 ^{MAPK的激活}和 JNK (p46/54)，以及 Akt 和 ERK1/2 的抑制作用。DrfL 还上调 GBM 细胞中的促凋亡蛋白（BNIP3 和 PUMA）和自噬蛋白（Atg5 和 LC3 裂解）。值得注意的是，抑制自噬和 caspase-8 都能够减轻用 DrfL 处理的 GBM 细胞的细胞死亡。我们的结果表明 DrfL 对 GBM 的细胞毒性涉及细胞通路的调节，包括 MAPK 和 Akt，它们与自噬和 caspase-8 依赖性细胞死亡有关。