联合应用树突体-姜黄素与多比环素协同抑制A549肺癌细胞的增殖、迁移，且诱导细胞凋亡。
Combined Treatment of Dendrosomal-Curcumin and Daunorubicin Synergistically Inhibit Cell Proliferation, Migration and Induce Apoptosis in A549 Lung Cancer Cells.
发表日期：2023 Jul
作者：
Seyed Sadegh Eslami, Davod Jafari, Abbas Ghotaslou, Moein Amoupour, Amir Asri Kojabad, Rasool Jafari, Navid Mousazadeh, Parastoo Tarighi, Majid Sadeghizadeh
来源：
GENES & DEVELOPMENT
摘要：
用于治疗肺癌的化疗药物与药物抗性和严重的副作用相关联。对于新的治疗候选药物和新方法，包括联合疗法，人们的需求不断增加。在这里，我们旨在研究一种姜黄素的树状体制剂（DNC）和丹奴霉素（DNR）对A549肺癌细胞系的联合作用。我们进行了细胞毒性、凋亡、细胞迁移、克隆形成能力和基因表达分析，解释了DNC和DNR对A549细胞的联合作用的机制。我们的结果显示，DNC和DNR的联合能够协同抑制A549细胞的生长。这种协同的细胞毒性在流式细胞术、迁移评估、克隆形成能力和基因表达分析中得到进一步验证。与单独使用DNR相比，DNC与DNR的联合治疗导致凋亡与坏死比例增加。此外，当DNC与DNR结合时，细胞迁移和克隆形成能力处于最低范围。联合治疗明显降低了MDR-1、hTERT和Bcl-2基因的表达水平。此外，Bax/Bcl2基因表达比例显著增加。我们通过自由姜黄素、树状体和DNC的分析也表明，树状体对A549细胞没有显著的细胞毒性作用，这表明这种载体在增强姜黄素的生物效应方面具有很高的潜力。我们的观察结果表明，DNC姜黄素制剂通过调节凋亡/坏死比例，以及Bax/Bcl2比例、MDR-1和hTERT基因表达，协同增强了DNR对A549细胞系的抗肿瘤效果。©2023 作者们。
Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line.We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells.Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells' growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of MDR-1, hTERT and Bcl-2 genes significantly. In addition, the ratio of Bax/Bcl2 gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin's biological effects.Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as Bax/Bcl2 ratio, MDR-1 and hTERT gene expression.©2023 The Authors.