Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway

GRP78: A cell's response to stress

“…Xie et al show that overexpression of GRP78 reduced the sensitivity of gemcitabine so it may have a critical role in the resistance of breast cancer cells. This reduction in sensitivity is caused by apoptosis inhibition [88]. The same group shows that caspase 9 and its phosphorylated form p37 were excessively down-regulated in GRP78-overexpressed breast cancer cells and was markedly increased in GRP78downregulated breast cancer cells [88].…”

“…These metabolites are combined with DNA to stop replication and cell growth leading to apoptosis [87]. The major problem that affects therapy is drug resistance [88]. GRP78 was demonstrated to promote drug resistance in breast cancer against doxorubicin [89].…”

“…On the other hand, the intrinsic pathway involves a series of events that are processed in the mitochondria [90]. Caspase 9 is triggered by the intrinsic pathway [91] and is found to be responsible for gemcitabine resistance and GRP78-regulated chemosensitivity [88]. Xie et al show that overexpression of GRP78 reduced the sensitivity of gemcitabine so it may have a critical role in the resistance of breast cancer cells.…”

“…This reduction in sensitivity is caused by apoptosis inhibition [88]. The same group shows that caspase 9 and its phosphorylated form p37 were excessively down-regulated in GRP78-overexpressed breast cancer cells and was markedly increased in GRP78downregulated breast cancer cells [88]. The levels of anti-apoptosis protein Bcl-2 is found to be high in GRP78-overexpressing breast cancer cells, on the other hand, the levels of pro-apoptosis proteins, Bax and Bim are low, and vice versa [88].…”

Lycorine Induces Apoptosis of A549 Cells via AMPK-Mammalian Target of Rapamycin (mTOR)-S6K Signaling Pathway

“…Research in mammalian systems found that inhibition of mTOR activated autophagy [19]. In addition, AMPK can change the conformational of pro-apoptotic protein Bax to maintain mitochondrial transmembrane potential (ΔΨm), blocking the release of cytochrome C and activation of caspase-3, which in turn inhibits apoptosis [20]. …”