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.
Article
in Zh
| WPRIM
| ID: wpr-254459
Responsible library:
WPRO
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>
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
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Phenanthrenes
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Poly(ADP-ribose) Polymerases
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Drug Resistance, Neoplasm
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BRCA2 Protein
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Cell Line, Tumor
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Drug Therapy
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Fanconi Anemia Complementation Group D2 Protein
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Poly(ADP-ribose) Polymerase Inhibitors
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Poly (ADP-Ribose) Polymerase-1
Limits:
Humans
Language:
Zh
Journal:
Chinese Journal of Medical Genetics
Year:
2014
Type:
Article