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Previous studies have shown that the effects of all-trans retinoic acid (ATRA) are mediated mainly through retinoic acid receptor alpha (RARα) and that the phosphorylation of a serine residue at amino acid 77 in the AF-1 domain of RARα was required for the basal activation function of RARα. In the present study, the effect of hypophosphorylated RARα(RARαS77A) in the proliferation of multiple myeloma(MM) was investigated.To determine whether RARαS77A would inhibit the proliferation of MM cells, RPMI8226 cells were transfected with constructing lentivirus-RARαS77A. The proliferation inhibition of ATRA and RARαS77A on MM cells were detectd by CCK-8. The molecular mechanisms of ATRA and RARαS77A on MM cells were explored by flow cytometer and western blotting.The proliferation of RPMI8226 cells was inhibited by ATRA in a dose- and time-dependent manner. Compared with the control group, ATRA significantly arrested the cell cycle at the G1 phase (P<0. 05). The proliferation of MM cells transfected with lentivirus-RARαS77A was significantly inhibited compared with cells transfected with the control vector (p<0. 05). In addition, G1 arrest was significantly observed in MM cells transfected with lentivirus-RARαS77A (p<0. 05). The expression levels of retinoblastoma protein (Rb) and caspase-3 in the ATRA-treated and lentivirus-RARαS77A-transfected groups were increased compared with the control group.RARαS77A could mimic the proliferation inhibition and apoptosis promotion effects of ATRA on human RPMI8226 myeloma cells. Similar to ATRA, RARαS77A could induce G1 arrest by increasing the expression levels of Rb and caspase-3 in the anti-proliferation of MM cells.No relevant conflicts of interest to declare.

Abstract 4990