Effect of PARP1 inhibitor PJ34 on multi-drug resistance in human multiple myeloma cell line and its relationship with FA/BRCA pathway / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 312-316, 2014.
Artigo
em Chinês
| WPRIM
| ID: wpr-254459
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of PARP1 inhibitor PJ34 on multi-drug resistance in a human multiple myeloma cell line and its connection with FA/BRCA pathway in DNA damage repair.</p><p><b>METHODS</b>A CCK8 assay was used to measure the inhibition rate. Real-time quantitative PCR was used to detect expression changes of DNA repair genes involved in the FA/BRCA pathway. Western blotting assay was used to detect expression of key protein FANCD2 in the FA/BRCA pathway. Annexin VFITC/PI double staining flow cytometry was used to measure cell apoptosis induced by PJ34. A COMET assay was used to detect the effect of PJ34 on DNA damage repair.</p><p><b>RESULTS</b>PJ34 could significantly enhance the sensitivity of RPMI8226/R cells to melphalan. The IC50 value of melphalan was dropped from 20.43 mol/L to 7.8 mol/L. PJ34 could inhibit the DNA damage repair, and the effect was related with the inhibition of FA/BRCA pathway. PJ34 and melphalan showed a synergistic effect in promoting the apoptosis of RPMI8226/R cells.</p><p><b>CONCLUSION</b>PJ34 can reverse the resistance of RPMI8226/R cells to melphalan by inhibiting the FA/BRCA pathway, which in turn can induce suppression of DNA damage repair. Therefore, PJ34 may have clinical value in overcoming the multi-drug resistance of multiple myeloma.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fenantrenos
/
Poli(ADP-Ribose) Polimerases
/
Resistencia a Medicamentos Antineoplásicos
/
Proteína BRCA2
/
Linhagem Celular Tumoral
/
Tratamento Farmacológico
/
Proteína do Grupo de Complementação D2 da Anemia de Fanconi
/
Inibidores de Poli(ADP-Ribose) Polimerases
/
Poli(ADP-Ribose) Polimerase-1
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Medical Genetics
Ano de publicação:
2014
Tipo de documento:
Artigo
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