Deactivation Of Cisplatin-resistant Lung Cancer Cells By Photodynamic Therapy Combined With Cisplatin

Background: Platinum-based antitumor drugs are among the first-line chemotherapeutic agents against a variety of solid tumors,but the drugresistance is the significant cause of chemotherapy failure.Novel strategies to overcome cisplatin resistance are highly desired.Photodynamic therapy(PDT)is a clinically approved cancer therapy,based on a photochemical reaction between a photosensitizer,light,and molecular oxygen.PDT is a two-stage procedure,which starts with photosensitizer administration followed by a appropriate light exposure to region tumor,with the aim of confined tumor destruction.Combinations of various therapies with nonoverlapping toxicities are among the commonly used strategies to improve the therapeutic effect in modern oncology.It is conceivable that resistance induced by one treatment might be overcome by another treatment.Objective: To explore the effect of pyropheophorbide-a methyl ester(MPPa)mediated photodynamic therapy(PDT)or combined with cisplatin(DDP)on chemoresistant human lung cancer cells.Methods: Human lung cancer cells A549 and A549/DDP were divided to control,DDP,PDT and PDT+DDP groups.Control group: cells were exposed no drugs;DDP group: cells were treated with 14 μmol/L DDP alone;PDT group: cells were treated with 2 μmol/L MPPa and 2.4 J/cm2 light;PDT+DDP group: cells were treated with PDT combined with DDP.Cell viability was determined with the CCK-8 assay,apoptosis was detected with the Annexin V-FITC/PI assay,and intracellular reactive oxygen species(ROS)was measured with the DCFH-DA assay.Western blot assay was performed to determine the expression of Caspase-3,Bcl-2 and Bax proteins.Results: PDT suppressed the cell viability in both cell lines,with the lowest percentage of survival cells noted in group PDT+DDP(P<0.05).The combination indexes were 1.11 and 1.10 in A549 and A549/DDP cells,respectively,indicating that the combination caused addition.The apoptosis rate in group PDT+DDP was higher than that in other group(P<0.05),so did ROS.The expression of Caspase-3 and Bax protein was increased and Bcl-2 protein was decreased in group PDT+DDP(P<0.05).Conclusion: PDT combined DDP can efficiently deactivate DDPresistant cancer cells via the mitochondria apoptosis pathway.The interaction between PDT and DDP was addition.