Interleukin-6 (IL6)-triggered JAK/STAT3 and PI3K/AKT signaling pathways are known to mediate cell survival, drug resistance and progression in a variety of cancer cells. Resistance to induction of apoptosis plays a critical role in the pathogenesis of numerous cancers and development of resistance to chemotherapeutic agents used in its treatment. Previous research in our laboratory employing a dexamethasone-resistant subline (7TD1-Dxm) of IL6-dependent 7TD1 cells indicated that constitutively activated STAT3 was important in control of apoptosis and targets downstream to activated STAT3 appeared to be involved in the development of resistance to dexamethasone by 7TD1 cells. We therefore investigated the hypothesis that Dxm-resistance developed by 7TD1-Dxm cells was due to resistance to induction of apoptosis mainly because of the dysregulation of the downstream targeted in JAK/STAT3 signaling pathway. Our results indicate that 7TD1-Dxm cells show resistance to Dxm-induced reduction of Bcl-2 protein and the release of cytochrome c. Thus, this study suggests that development of resistance to dexamethasone by 7TD1 cells may involve altered regulation of mitochondrial anti-apoptotic proteins.
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