丹皮酚非离子表面活性剂囊泡体外协同5-氟尿嘧啶抗肝癌HepG2细胞作用研究

Study on the Synergistic Antitumor Effects with 5-Fu of Pae-PEG-NISVs Against HepG2 Cells in Vitro

目的:在前期制备丹皮酚非离子表面活性剂囊泡(Pae-PEG-NISVs)的基础上,考察其对于肿瘤细胞的抑制作用和抗增殖作用,以及与5-氟尿嘧啶(5-Fu)联用时对Hep G2细胞杀伤作用。方法:通过MTT法观察丹皮酚非离子表面活性剂囊泡对Hep G2细胞的毒性,采用荧光染色考察Pae-PEG-NISVs对Hep G2细胞凋亡的研究,采用生长抑制实验考察Pae-PEGNISVs和化疗药物5-Fu联合作用时对Hep G2细胞的抗增殖作用能否产生协同效应。结果:体外抗肿瘤试验显示空白囊泡(PEG-NISVs)无显著细胞毒性。与丹皮酚溶液组相比,Pae-PEG-NISVs抑制肿瘤细胞Hep G2增殖和促进其凋亡效果更显著,并且呈现剂量依赖形式。此外,还研究了Pae-PEG-NISVs与丹皮酚溶液和化疗药物联用时对于肿瘤细胞的抑制作用,发现不同浓度的PEG-PAE-NISVs和低浓度的5-Fu联用时,相互作用指数小于1,说明两药联用对促进肿瘤凋亡并抑制其增殖会产生协同作用。结论:PEG-Pae-NISVs较丹皮酚溶液能够明显增强对肿瘤细胞的杀伤作用,有望作为新型的抗肿瘤药物递送系统。

Objective:To observe the inhibition and anti-proliferative effects on tumor cells of the Pae-PEG-NISVs prepared in the early stage of the research group and its synergistic antitumor effects with 5-fluorouracil(5-Fu).Methods:The cytotoxicity of Pae-PEG-NISVs was investigated against HepG2 cells by MTT assay.Fluorescence staining was used to detect the apoptotic morphological changes.Then growth inhibition assays were carried out to investigate whether Pae-PEG-NISVs could enhance the antiproliferative effects of Pae co-treated with 5-Fu on HepG2 cells.Results:PEG-NISVs showed no significant cytotoxicity in vitro anti-tumor tests.Pae-PEG-NISVs were more significant in inhibiting the proliferation of HepG2 cells and promoting their apoptosis,and this phenomenon showed a dose-dependent trend.In addition,the combined effect of free and formulated Paeonol with Chemotherapy drugs(5-Fu)was examined,and it was found that PEG-Pae-NISVs and low concentrations of 5-Fu were obviously synergistic with coefficient of drug interaction value less than 1,which indicated that the combination of the two drugs can promote synergistic effect on promoting tumor apoptosis and inhibiting the proliferation of tumor cells.Conclusions:PEG-PAE NISVs can significantly enhance the antitumor effects compared with paeonol solution,and it is expected to be a new delivery system of anti-tumor drugs.