PJ34, a poly(ADP-ribose) polymerase (PARP) inhibitor, reverses melphalan-resistance and inhibits repair of DNA double-strand breaks by targeting the FA/BRCA pathway in multidrug resistant multiple myeloma cell line RPMI8226/R.

摘要: Abstract There is still no ideal treatment for multidrug resistant multiple myeloma, looking drugs which can reverse chemotherapy resistance and enhance curative effects of becomes a problem that needs to be solved urgently. Poly(ADP-ribose) polymerase inhibitors appear an important tool medical therapy several malignancies. In the present study, we investigated potential PARP-1 inhibitor PJ34, in vitro, further efficacy traditional drug melphalan in multidrug-resistant myeloma cell line RPMI8226/R. The different concentrations PJ34 on proliferation were determined by CCK-8 assay. expressions FA/BRCA pathway-related factors detected western blotting RT-PCR. percentage apoptosis was measured with flow cytometry. DNA double-strand break (DSB) repair quantified γH2AX immunofluorescence. addition, damage at level individual comet Co-administration had synergistic inhibitory RPMI8226/R cells, suggesting more powerful antitumor activities. also increased obviously plus PJ34. activation pathway inhibited downregulation related including FANCD2, BRCA2 Rad51. significantly ratio γH2AX-positive cells number foci/cells. tail rate length, moment Olive all after cells. These results indicate combined produces reverses effectively. cannot induce directly, but it may increase induced through inhibiting repair. suppression mechanism. Therefore, suggest PARP deserve future investigations as tools myeloma.