title: Killing effect of Ad5/F35-APE1 siRNA recombinant adenovirus in combination with hematoporphrphyrin derivative-mediated photodynamic therapy on human nonsmall cell lung cancer.
abstract: 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.
authors.affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.forename: Wei
authors.initials: W
authors.lastname: Guan
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Yun-Song
authors.initials: YS
authors.lastname: Zhang
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Zeng
authors.forename: Zeng-Peng
authors.initials: ZP
authors.lastname: Li
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy; D010778:Photochemotherapy / Q000379:methods; D034741:RNA, Small Interfering / Q000378:metabolism*; D017382:Reactive Oxygen Species
chemical_list: D006415:Hematoporphyrins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase