PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus

摘要: Recently, much progress has been achieved in the treatment of multiple myeloma (MM). However, major challenge chemotherapeutic drugs is acquired resistance. Oncolytic virotherapies offer promising alternatives; with possibility their integration current therapeutic strategies. In present study, we assessed potential ZD55-TRAIL (an oncolytic adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand) as an agent for MM. Our results clearly indicated that ZD55 armed TRAIL was more cytotoxic to drug-sensitive well drug-resistant MM cell lines, than virus alone. Furthermore, it also observed induced apoptosis through activation caspase pathway. particular, significantly inhibited insulin-like growth factor-1 receptor (IGF-1R) and NFκB. IGF did not abrogate ZD55‑TRAIL-induced death. Combination PI3K inhibitor LY294002 RPMI‑8226 cells virus‑mediated mTOR AKT, thus, promoting Combined MG132 (a proteasome inhibitor) robustly increased expression death 5 (DR5), which enhanced response without significant toxicity normal liver cells. Collectively, our suggest combined TRAIL-armed a or proteosome may serve therapy