Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells.
Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells.
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DOI：
10.31557/apjcp.2019.20.7.2225
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发表时间：
2019-07-01
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影响因子：
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通讯作者：
Ahmed, Hanaa H
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文献类型：
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作者：
Abd-Rabou, Ahmed A;Ahmed, Hanaa H
非小细胞肺癌（NSCLC）和肝细胞癌（HCC）在世界各地的某些人群中非常常见。尽管最近在诊断和治疗方面取得了进展，但由于耐药性的发展，其预后仍然很差。尽管阿霉素 (DOX) 被认为是抗实体瘤药物效果最强的药物之一，但耐药性的产生导致了不成功的结果。当前研究的基本原理是探索使用抗癌药物对 DOX 处理的癌细胞的致敏能力；贝伐珠单抗（阿瓦斯汀；AV）和 CCR2 抑制剂（CR）的游离制剂和纳米制剂。在此，测量了合成纳米粒子的平均尺寸、多分散指数（PDI）、zeta电位和包埋效率（EE%）。我们研究了这些平台对人 HCC（HepG2 和 Huh-7）和 NSCLC (A549) 癌细胞系的增殖、凋亡、坏死、一氧化氮 (NO)、丙二醛 (MDA) 和锌水平的影响。在治疗过程中测试了使用 Huh-7 和 A549 癌细胞的葡萄糖消耗率。我们证明 AV 和 CR 纳米治疗显着抑制 A549 细胞活力并通过 NO 水平升高激活细胞凋亡。我们得出结论，AVCR NP plusDOX 比 Huh-7 和 HepG2 细胞更能显着诱导 A549 细胞毒性介导的细胞凋亡。这种药物-药物组合比 HepG2 细胞更能诱导 Huh-7 细胞毒性介导的细胞凋亡。总之，AVCR NP 通过活性氧 (ROS) 刺激细胞凋亡来使 DOX 处理的 A549 和 Huh-7 细胞变得敏感。总而言之，我们的数据表明 CR 加 AV 纳米平台将成为在不久的将来治疗 CCR2 阳性 NSCLC 和 HCC 患者的潜在个性化医学策略。
Non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) are very common in certain populationaround the world. Despite the recent advances in their diagnosis and therapy, their prognosis remains poor due to thedevelopment resistance to drug. Although doxorubicin (DOX) is considered to be one of the most anti-solid tumordrugs, developed resistance is contributing to unsuccessful outcome. The rationale of the current study is to explorethe sensitizing capability of the DOX-treated cancer cells using the anticancer agents; bevacizumab (avastin; AV) andCCR2 inhibitor (CR) in their free- and nano-formulations. Here, the average size, polydispersity index (PDI), zetapotential, and entrpment effeciency (EE%) of the synthesized nanoparticles were measured. We investigated the effectof these platforms on the proliferation, apoptosis, necrosis, nitric oxide (NO), malondialdehyde (MDA), and zinc levelsof human HCC (HepG2 and Huh-7) and NSCLC (A549) cancer cell lines. Glucose consumption rates using Huh-7and A549 cancer cells were tested upon treatments. We demonstrated that AV and CR nano-treatments significantlysuppressed A549 cell viability and activated apoptosis by NO level elevation. We concluded that AVCR NP plusDOX significantly induces A549 cytotoxicity-mediated apoptosis more than Huh-7 and HepG2 cells. This drug-drugnano-combination induced Huh-7 cytotoxicity-mediated apoptosis more than HepG2 cells. In conclusion, AVCR NPsensitized DOX-treated A549 and Huh-7 cells through reactive oxygen species (ROS)-stimulated apoptosis. Takentogether, our data suggested that the CR plus AV nano-platforms would be a potential personalized medicine-basedstrategy for treating CCR2-positive NSCLC and HCC patients in the near future.