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  • Title: [Effect of PARP1 inhibitor PJ34 on multi-drug resistance in human multiple myeloma cell line and its relationship with FA/BRCA pathway].
    Author: Xiong T, Wei H, Chen X, Xiao H.
    Journal: Zhonghua Yi Xue Yi Chuan Xue Za Zhi; 2014 Jun; 31(3):312-6. PubMed ID: 24928009.
    Abstract:
    OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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