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首页> 美国卫生研究院文献>Molecules >Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2
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Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2

机译：巴西绿蜂胶提取物通过增强原卟啉IX的细胞内蓄积和减弱NF-κB和COX-2与原卟啉IX介导的光动力疗法协同作用。

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Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo.
机译：巴西绿色蜂胶（BGP）因其令人印象深刻的抗肿瘤作用而闻名，并已在多种文化中用作民间药物多年。已经证明BGP可以增强细胞生长抑制药物对肿瘤细胞的细胞毒性作用。光动力疗法（PDT）是一种针对恶性细胞的治疗方法。为了评估BGP提取物对原卟啉IX（PpIX）介导的光细胞毒性的协同作用，使用A431和HeLa细胞进行了MTT分析。进行TUNEL测定和膜联蛋白V-FITC / PI染色以证实细胞凋亡的诱导。进行蛋白质印迹分析以检查A431细胞中的促凋亡蛋白，抗凋亡蛋白和炎症相关蛋白。通过流式细胞术检查PpIX的细胞内积累。还用异种移植模型评估了BGP提取物在PpIX-PDT中的协同作用。我们的发现表明，BGP提取物增加了A431和HeLa细胞中PpIX介导的光细胞毒性。用BGP提取物处理的PpIX-PDT导致Bcl-xL减少，NOXA，Bax和caspase-3裂解增加。 PpIX-PDT上调了p-IKKα/β，NF-κB和COX-2的蛋白表达水平，但与BGP提取物联合使用时，其蛋白表达水平明显降低。还发现BGP提取物可显着增强A431细胞中PpIX的细胞内积累。 BGP提取物在异种移植模型中也增加了PpIX介导的光细胞毒性。我们的发现为体外和体内PpIX-PDT中BGP提取物的协同作用提供了证据。

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