Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Department of Oncology, Cancer Hospital, Chongqing, 400030, China.
Sci Rep. 2017 Aug 11;7(1):7965. doi: 10.1038/s41598-017-06086-2.
Chemotherapy plays a significant role in glioma treatment; however, it has limited effectiveness in extending the life expectancies of glioma patients. Traditional studies have attributed this lack of efficacy to glioma stem cells (GSCs) and their high resistance to chemotherapy, and hypoxia worsens this issue. In contrast, hyperoxia effectively alleviates hypoxia in glioma and sensitizes glioma cells to chemotherapy. In a summary of traditional studies, the majority of researchers overlooked the influence of hypoxia on differentiated cells because they only focused on the maintenance of GSCs stemness, which thus resulted in chemoresistance. Because of this background, we hypothesized that GSCs may be induced through dedifferentiation under hypoxic conditions, and hypoxia maintains GSCs stemness, which thus leads to resistance to chemotherapy. In contrast, hyperoxia inhibits the dedifferentiation process and promotes GSCs differentiation, which increases the sensitization of glioma cells to chemotherapy. Hypoxia-inducible factor-1α (HIF1α) contributes substantially to the stemness maintenance of GSCs and resistance of glioma to chemotherapy; thus, we investigated whether HIF1α regulates the resistance or sensitization of glioma cells to chemotherapy in different oxygen levels. It highlights a novel viewpoint on glioma chemosensitivity from the transformation between dedifferentiation and differentiation in different oxygen levels.
化疗在胶质瘤治疗中起着重要作用；然而，它在延长胶质瘤患者的预期寿命方面效果有限。传统研究将这种疗效不足归因于胶质瘤干细胞（GSCs）及其对化疗的高度耐药性，而缺氧会使问题恶化。相比之下，高氧有效地缓解了胶质瘤中的缺氧，并使胶质瘤细胞对化疗敏感。在对传统研究的总结中，大多数研究人员忽略了缺氧对分化细胞的影响，因为他们只关注 GSCs 干性的维持，从而导致了耐药性。基于这一背景，我们假设 GSCs 可能在缺氧条件下通过去分化诱导，而缺氧维持 GSCs 的干性，从而导致对化疗的耐药性。相比之下，高氧抑制去分化过程并促进 GSCs 分化，从而增加了胶质瘤细胞对化疗的敏感性。缺氧诱导因子-1α（HIF1α）对 GSCs 的干性维持和胶质瘤对化疗的耐药性有重要贡献；因此，我们研究了 HIF1α 是否在不同氧水平下调节胶质瘤细胞对化疗的耐药性或敏感性。它从不同氧水平下的去分化和分化之间的转化，为胶质瘤的化疗敏感性提供了一个新的观点。
