关键词: Apoptosis Cytometry. Flow Lung cancer Reactive oxygen species Sanguinarine Vegf

Mesh : Humans Lung Neoplasms / drug therapy Apoptosis Benzophenanthridines / pharmacology therapeutic use Antineoplastic Agents / pharmacology therapeutic use Oxidative Stress Isoquinolines

来  源:   DOI:10.2174/0118761429269383231119062233

Abstract:
BACKGROUND: Lung cancer (LC) incidence is rising globally and is reflected as a leading cause of cancer-associated deaths. Lung cancer leads to multistage carcinogenesis with gradually increasing genetic and epigenetic changes.
OBJECTIVE: Sanguinarine (sang) mediated the anticancer effect in LCC lines by involving the stimulation of reactive oxygen species (ROS), impeding Bcl2, and enhancing Bax and other apoptosis-associated protein Caspase-3, -9, and -PARP, subsequently inhibiting the LC invasion and migration.
OBJECTIVE: This study was conducted to investigate the apoptotic rate and mechanism of Sang in human LC cells (LCC) H522 and H1299.
METHODS: MTT assay to determine the IC50, cell morphology, and colony formation assay were carried out to show the sanguinarine effect on the LC cell line. Moreover, scratch assay and transwell assay were performed to check the migration. Western blotting and qPCR were done to show its effects on targeted proteins and genes. ELISA was performed to show the VEGF effect after Sanguinarine treatment. Immunofluorescence was done to check the interlocution of the targeted protein.
RESULTS: Sang significantly inhibited the growth of LCC lines in both time- and dose-dependent fashions. Flow cytometry examination and Annexin-V labeling determined that Sang increased the apoptotic cell percentage. H522 and H1299 LCC lines treated with Sang showed distinctive characteristics of apoptosis, including morphological changes and DNA fragmentation.
CONCLUSIONS: Sang exhibited anticancer potential in LCC lines and could induce apoptosis and impede the invasion and migration of LCC, emerging as a promising anticancer natural agent in lung cancer management.
摘要:
背景:肺癌(LC)发病率在全球范围内正在上升,并被反映为癌症相关死亡的主要原因。肺癌导致多阶段癌变,遗传和表观遗传变化逐渐增加。
目的:血根碱(sang)通过刺激活性氧(ROS)介导LCC系的抗癌作用,阻碍Bcl2,并增强Bax和其他凋亡相关蛋白Caspase-3,-9和-PARP,随后抑制LC的入侵和迁移。
目的:本研究旨在研究Sang在人LC细胞(LCC)H522和H1299中的凋亡率和机制。
方法:MTT法测定IC50,细胞形态,进行集落形成测定以显示血根碱对LC细胞系的作用。此外,进行划痕测定和transwell测定以检查迁移。进行Western印迹和qPCR以显示其对靶向蛋白质和基因的影响。进行ELISA以显示血根碱处理后的VEGF作用。进行免疫荧光以检查目标蛋白的位置。
结果:Sang以时间和剂量依赖性方式显着抑制LCC系的生长。流式细胞术检查和膜联蛋白-V标记确定Sang增加了凋亡细胞百分比。用Sang处理的H522和H1299LCC细胞系表现出独特的凋亡特征,包括形态变化和DNA片段化。
结论:Sang在LCC细胞系中具有抗癌潜力,可诱导细胞凋亡并阻止LCC的侵袭和迁移。正在成为肺癌治疗中一种有前途的抗癌天然药物。
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