目的:研究聚腺苷酸二磷酸核糖转移酶-1(PARP-1)抑制剂PJ34对人肝癌细胞株HepG2增殖的影响及其作用机制,以及PJ34是否进一步增强γ射线对肝癌细胞的增殖抑制作用.方法:细胞增殖实验观察不同浓度的PJ34,以及PJ34合并γ射线照射对HepG2细...目的:研究聚腺苷酸二磷酸核糖转移酶-1(PARP-1)抑制剂PJ34对人肝癌细胞株HepG2增殖的影响及其作用机制,以及PJ34是否进一步增强γ射线对肝癌细胞的增殖抑制作用.方法:细胞增殖实验观察不同浓度的PJ34,以及PJ34合并γ射线照射对HepG2细胞增殖的影响,流式细胞仪检测PJ34对HepG2细胞凋亡的影响.结果:PJ34对HepG2细胞的增殖有显著的抑制作用(t=15.175,P<0.01).随着PJ34浓度的增加,其抑制作用进一步增强.1Gy的γ射线照射对HepG2细胞的增殖有明显抑制作用,但γ射线照射联合PJ34与单用PJ34或γ射线照射对肝癌细胞的增殖抑制作用相比较无明显统计学差异(t=-1.413,P>0.05).PJ34能诱导HepG2细胞凋亡,72h时凋亡率明显高于对照组,二者有显著性差异(33.2% vs 11.4%,P<0.01).结论:PARP-1抑制剂PJ34通过诱导HepG2细胞凋亡抑制人肝癌细胞的增殖;PJ34并不显著增加γ射线对HepG2细胞增殖的抑制作用.展开更多
Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect o...Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines （HepG2, Hep3B and HCC-LM3） treated with PJ34 （8 μmol/L） and SAHA （1 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing subcutaneous HepG2 tumors were administered different groups of drugs （10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34＋25 mg/kg SAHA）, and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of P J34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34＋SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone （P〈0.05）. In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34＋SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.展开更多
Poly （ADP-ribose） polymerase-I （PARP-1） plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relation...Poly （ADP-ribose） polymerase-I （PARP-1） plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ische- mia-reperfusion induced cell death has triggered more and more attention. Here, we examined the pro- tective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion （OGDR） model of primary rat astrocytes in vitro, which could mimic the ische- mia-reperfusion damage in the ＂ischemic core＂. Meanwhile, cell death pathways of various P J34 treated astrocytes were also investigated. Our results showed that P J34 incubation （10 μmol/L） did not affect release of lactate dehydrogenase （LDH） from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, P J34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apop- totic rate. The intervention timing study demonstrated that an earlier and longer P J34 intervention dur- ing reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the ＂ischaemic core＂ mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.展开更多
文摘目的:研究聚腺苷酸二磷酸核糖转移酶-1(PARP-1)抑制剂PJ34对人肝癌细胞株HepG2增殖的影响及其作用机制,以及PJ34是否进一步增强γ射线对肝癌细胞的增殖抑制作用.方法:细胞增殖实验观察不同浓度的PJ34,以及PJ34合并γ射线照射对HepG2细胞增殖的影响,流式细胞仪检测PJ34对HepG2细胞凋亡的影响.结果:PJ34对HepG2细胞的增殖有显著的抑制作用(t=15.175,P<0.01).随着PJ34浓度的增加,其抑制作用进一步增强.1Gy的γ射线照射对HepG2细胞的增殖有明显抑制作用,但γ射线照射联合PJ34与单用PJ34或γ射线照射对肝癌细胞的增殖抑制作用相比较无明显统计学差异(t=-1.413,P>0.05).PJ34能诱导HepG2细胞凋亡,72h时凋亡率明显高于对照组,二者有显著性差异(33.2% vs 11.4%,P<0.01).结论:PARP-1抑制剂PJ34通过诱导HepG2细胞凋亡抑制人肝癌细胞的增殖;PJ34并不显著增加γ射线对HepG2细胞增殖的抑制作用.
基金supported by grants from the National Natural Science Foundation of China(No.81172293)the New Century Excellent Talent Foundation of Ministry of Education of China(No.NCET-04-0701)
文摘Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines （HepG2, Hep3B and HCC-LM3） treated with PJ34 （8 μmol/L） and SAHA （1 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing subcutaneous HepG2 tumors were administered different groups of drugs （10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34＋25 mg/kg SAHA）, and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of P J34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34＋SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone （P〈0.05）. In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34＋SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.
基金supported by the National Natural Science Foundation of China(No.30971024)
文摘Poly （ADP-ribose） polymerase-I （PARP-1） plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ische- mia-reperfusion induced cell death has triggered more and more attention. Here, we examined the pro- tective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion （OGDR） model of primary rat astrocytes in vitro, which could mimic the ische- mia-reperfusion damage in the ＂ischemic core＂. Meanwhile, cell death pathways of various P J34 treated astrocytes were also investigated. Our results showed that P J34 incubation （10 μmol/L） did not affect release of lactate dehydrogenase （LDH） from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, P J34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apop- totic rate. The intervention timing study demonstrated that an earlier and longer P J34 intervention dur- ing reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the ＂ischaemic core＂ mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.
