This study aimed to investigate the effect of Catharanthus roseus L. (C. roseus) leaf extract on the migration and invasion of MDA-MB-231 cell line and elucidate the molecular mechanisms of action. Effect of the extract on cell viability was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl2H-tetrazoliumbromide) assay. Anti-migratory and anti-invasive effects were evaluated using scratch and Transwell assays. Effect on the levels and activities of matrix metalloproteinase (MMP)-2 and MMP-9 was determined using ELISA and gelatin zymography. Furthermore, changes in the expression of 84 genes commonly involved in cell motility were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and cell motility RT² profiler PCR array. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID. Using STRING and Cytoscape software, hub genes were determined. The extract significantly (p < 0.001) inhibited the migration and invasion of MDA-MB-231 cells at non-cytotoxic concentrations. The activities and levels of MMP-2 and MMP-9 were decreased in a dose-dependent manner following C. roseus exposure. At 4 µg/mL, the extract significantly downregulated the expression of 52 genes involved in extracellular matrix degradation, cytoskeleton reorganisation, focal adhesions and invadopodia formation. GO and KEGG pathway analysis revealed that the downregulated genes were significantly enriched in biological processes and pathways closely related to cell motility. Our findings showed that C. roseus inhibited the migration and invasion of MDA-MB-231 cells through altering the expression of various motility-related genes. This study provided data about the potential of C. roseus phytochemicals as promising therapeutic agents against breast cancer metastasis, especially at gene level.

这项研究旨在研究长春花（C. roseus）叶提取物对MDA-MB-231细胞系迁移和侵袭的影响，并阐明其作用的分子机制。通过MTT（3-（4,5-二甲基-2-噻唑基）-2,5-二苯基2H-四唑溴化物）测定法评估提取物对细胞存活力的影响。使用划痕和Transwell分析评估了抗迁移和抗侵袭作用。用ELISA和明胶酶谱法测定对基质金属蛋白酶（MMP）-2和MMP-9水平和活性的影响。此外，通过逆转录聚合酶链反应（RT-PCR）和细胞运动RT ²评估了通常与细胞运动有关的84个基因的表达变化。Profiler PCR阵列。使用DAVID进行了基因本体论（GO）和《京都基因与基因组百科全书》（KEGG）途径分析。使用STRING和Cytoscape软件，确定轮毂基因。该提取物 在非细胞毒性浓度下显着（p <0.001）抑制了MDA-MB-231细胞的迁移和侵袭。玫瑰色念珠菌后MMP-2和MMP-9的活性和水平呈剂量依赖性降低接触。在4 µg / mL的浓度下，提取物显着下调了与细胞外基质降解，细胞骨架重组，粘着斑和侵袭伪足形成有关的52个基因的表达。GO和KEGG通路分析表明，下调的基因在与细胞运动密切相关的生物过程和通路中显着丰富。我们的发现表明，玫瑰色念珠菌通过改变各种运动相关基因的表达来抑制MDA-MB-231细胞的迁移和侵袭。这项研究提供了有关玫瑰花念珠菌植物化学物质作为抗乳腺癌转移的有前景治疗剂的潜力的数据，尤其是在基因水平上。