Killing effect of Ad5/F35-APE1 siRNA recombinant adenovirus in combination with hematoporphrphyrin derivative-mediated photodynamic therapy on human nonsmall cell lung cancer.

Killing effect of Ad5/F35-APE1 siRNA recombinant adenovirus in combination with hematoporphrphyrin derivative-mediated photodynamic therapy on human nonsmall cell lung cancer.
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DOI:
10.1155/2013/957913
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发表时间:
2013
影响因子:
--
通讯作者:
Yang ZZ
Yang ZZ
中科院分区:
生物学3区
文献类型:
--
作者:
Xia L;Guan W;Wang D;Zhang YS;Zeng LL;Li ZP;Wang G;Yang ZZ

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本研究的主要目的是探讨Ad 5/F35-APE 1 siRNA重组腺病毒联合血卟啉衍生物(HpD)介导的光动力疗法(PDT)对人肺腺癌A549细胞的体外杀伤作用及其分子机制,为HpD-PDT治疗肺癌提供理论参考。通过MTT、流式细胞术、ELISA和western blot等技术,观察到HpD-PDT对A549细胞的增殖抑制和凋亡作用,与对照组相比,差异有统计学意义(P < 0.05)。HpD浓度和激光强度对HpD的抑制效率有影响。Ad 5/F35-APE 1 siRNA与PDT联合应用后对A549细胞增殖的抑制作用更明显,细胞内ROS水平和炎性因子的表达明显升高(P <0. 05)。HpD-PDT诱导A549细胞APE 1蛋白表达在24 h后达到高峰。Ad 5/F35-APE 1 siRNA重组腺病毒(10 MOI)感染A549细胞48 h后,APE 1表达的抑制作用最明显。结论:Ad 5/F35-APE 1 siRNA重组腺病毒能有效抑制HpD-PDT诱导的APE 1表达,从而显著增强HpD-PDT对肺癌细胞的杀伤作用。
The main goal of this work is to investigate the killing effects and molecular mechanism of photodynamic therapy (PDT) mediated by the Ad5/F35-APE1 siRNA recombinant adenovirus in combination with a hematoporphrphyrin derivative (HpD) in the A549 human lung adenocarcinoma cell line in vitro to provide a theoretical reference for treating lung cancer by HpD-PDT. By using the technologies of MTT, flow cytometry, ELISA, and western blot, we observed that the proliferation inhibition and apoptosis of the A549 cells were significantly higher than the control group (P < 0.05) after HpD-PDT was performed. The inhibitory efficiency is dependent on the HpD concentration and laser intensity dose. The inhibitory effect on the proliferation of A549 cells of Ad5/F35-APE1 siRNA is more significant after combining with PDT, as indicated by a significant elevation of the intracellular ROS level and the expression of inflammatory factors (P < 0.05). The HpD-PDT-induced expression of the APE1 protein reached the peak after 24 h in A549 cells. The inhibition of APE1 expression in A549 cells was most significant after 48 hours of infection by Ad5/F35-APE1 siRNA recombinant adenovirus (10 MOI). In conclusion, the Ad5/F35-APE1 siRNA recombinant adenovirus could efficiently inhibit the HpD-PDT-induced APE1 expression hence could significantly enhance the killing effect of HpD-PDT in lung cancer cells.
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