Abstract
BackgroundThis study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin’s lymphoma (T-NHL), as well as the underlying molecular mechanisms.MethodsExpression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T-NHL tissues (n = 30) and normal lymph node tissues (n = 16) using western blot, real-time PCR and immunohistochemistry. Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia. Additionally, the proliferation and apoptosis of Hut-78 cells exposed to different concentration of Adriamycin (ADM) in normoxia and hypoxia were evaluated by MTT and Annexin-V FITC/PI staining assay. Finally, the effects of AEG-1 on Hut-78 cells exposed to ADM in hypoxia were assessed by MTT and Annexin-V FITC/PI staining assay, and 3-MA (autophagy inhibitor) was further used to determine the underlying mechanism.ResultsAEG-1, LC3-II and Beclin-1 expression were significantly increased in T-NHL tissues compared with normal tissues. Incubation of Hut-78 and Jurkat cells in hypoxia obviously increased AEG-1, LC3-II and Beclin-1 expression. Hypoxia induced proliferation and reduced apoptosis of Hut-78 cells exposed to ADM. AEG-1 overexpression further increased proliferation and decreased apoptosis of Hut-78 cells exposed to ADM in hypoxia. Moreover, overexpression of AEG-1 significantly inversed 3-MA induced-changes in cell proliferation and apoptosis of Hut-78 cells exposed to ADM in hypoxia.ConclusionsThis study suggested that AEG-1 is associated with hypoxia-induced T-NHL chemoresistance via regulating autophagy, uncovering a novel target against hypoxia-induced T-NHL chemoresistance.
Highlights
This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia inducedchemoresistance in T-cell non-Hodgkin’s lymphoma (T-NHL), as well as the underlying molecular mechanisms
AEG-1, LC3-II, Beclin-1, and Hypoxia inducible factor (HIF-1α) are significantly up-regulated in T-NHL tissues To examine the expression of AEG-1 in T-NHL, tumor tissues (n = 30) and normal lymph node tissues (n = 16) were first employed and analyzed by RT-PCR and western blot
Western blot analysis revealed the elevated levels of autophagy-related markers LC3-II and Beclin-1 in T-NHL tissues (Fig. 1b)
Summary
This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia inducedchemoresistance in T-cell non-Hodgkin’s lymphoma (T-NHL), as well as the underlying molecular mechanisms. The lymphoma, a type of blood cancer, is roughly classified as Hodgkin’s lymphoma (HD) and non-Hodgkin’s lymphoma (NHL), and NHL represents the most common malignancy (Hadzipecova et al, 2007). Chemotherapy still remains the major choice for the treatment of T-NHL, especially at the advanced stages, but T-NHL is not that sensitive to conventional chemotherapy (R et al, 1987). These chemotherapy options yield poor outcomes in T-NHL patients, mainly resulted from the chemoresistance development of T-NHL. More than 90% of deaths from cancer are associated with drug resistance and metastasis (Ahmad et al, 2012).
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