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Medientyp:
E-Artikel
Titel:
Abstract 316: Modifying autophagy through combination treatments as a potential therapeutic strategy in head and neck squamous cell carcinoma (HNSCC)
Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Introduction: Autophagy, a catabolic process, can play a crucial role in cancer cell survival. Modifying this process has shown to be an effective mechanism of inducing cell death. In order to explore this concept, we induced autophagy with one agent (Akt-inhibitor MK-2206), and decreased autophagosomal trafficking with other agents (Paclitaxel and Nocadazole) by disrupting the microtubule networks. We hypothesized that by modifying autophagy through this combination, it would lead to an accumulation of autophagosomes and eventual cell death in a synergistic manner.</jats:p>
<jats:p>Methods: SCC 61 and Cal 27 HNSCC cell lines were used to explore this hypothesis. SCC 61 cells were transduced with an m-Cherry GFP LC3B vector in order to detect autophagosomes under both fixed and live cell confocal microscopy. Cell viability and apoptosis assays were performed. A siRNA ATG 7 KO SCC 61 cell line was used to detect if in fact autophagy was important for this therapeutic approach.</jats:p>
<jats:p>Results: There was an accumulation of autophagosomes with the combination of an Akt inhibitor and microtubule disrupters. A decrease in fusion of autophagosome to lysosome was seen when cells were treated with an agent, which disrupted the microtubule networks (Paclitaxel) but even more dramatically when treated with the combination (MK-2206 and Paclitaxel). Moreover, accumulation of autophagosomes occurred prior to induction of apoptosis with combination treatment. These effects were decreased with siRNA ATG 7 KO in SCC 61 cells, which were more resistant to combination treatment compared to control.</jats:p>
<jats:p>Discussion: Manipulating autophagy with Akt inhibition (induction) and Paclitaxel (decreasing autophagic trafficking) leads to an accumulation of autophagosomes and eventual cell death in a synergistic manner. This therapeutic approach of altering the normal autophagic process warrants further investigation.</jats:p>
<jats:p>Citation Format: Omar G. Ahmed, Wen-Liang Kuo, Tai-Fen Wei, Jeannette S. Messer, Marina Sharifi, Madhavi Nagilla, Kay Macleod, Ezra E.W. Cohen. Modifying autophagy through combination treatments as a potential therapeutic strategy in head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 316. doi:10.1158/1538-7445.AM2014-316</jats:p>