通过木犀草素和紫杉醇的协同作用增强 MDA-MB-231 三阴性乳腺癌细胞的凋亡作用。
Enhanced Apoptotic Effects in MDA-MB-231 Triple-Negative Breast Cancer Cells Through a Synergistic Action of Luteolin and Paclitaxel.
发表日期:2024 Jul
作者:
Shabnam Tamanna, Elumalai Perumal, Jeevitha Rajanathadurai
来源:
Cellular & Molecular Immunology
摘要:
根据2020年癌症发病率报告,乳腺癌已成为全球女性第一大恶性肿瘤。这种多步骤疾病涉及遗传和环境因素。紫杉醇是一种天然存在的抗有丝分裂物质,是一种广泛使用的化疗药物,用于治疗各种人类恶性肿瘤,包括乳腺癌。然而,其主要缺点是其广泛的毒性。这种限制可以通过与木犀草素等天然产品的联合治疗来缓解。研究表明,木犀草素具有抗癌特性,因为它可以抑制癌细胞生长并诱导乳腺癌、肺癌和结肠癌的细胞凋亡。本研究旨在探讨木犀草素和紫杉醇联合使用对乳腺癌细胞的协同抗癌作用。本研究使用乳腺癌细胞系(MDA-MB-231)。然后进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)测定以检查细胞活力。随后在相差显微镜下进行形态学研究。形态学分析显示,当用 IC50 值的组合处理时,细胞出现明显的收缩和膜起泡,表明细胞凋亡。基因表达结果显示 B 细胞淋巴瘤 2 (BCL-2) 抗凋亡基因显着下调,进一步证实了其抗癌特性。这些发现表明,木犀草素-紫杉醇组合发挥协同作用,增强乳腺癌细胞的抗癌活性。进行逆转录聚合酶链反应(RT-PCR)来分析与细胞凋亡相关的基因。最后,对收集的数据进行统计分析,以证实研究的可靠性。 1 μM/ml 紫杉醇与增加浓度的木犀草素的组合显示细胞活力大幅降低,木犀草素浓度的 IC50 值约为 40 μM /毫升。形态学研究表明,在 40 μM/ml 处理后,癌细胞出现收缩和起泡。在相同的 IC50 浓度下,与单独使用木犀草素相比,木犀草素和紫杉醇联合使用可导致乳腺癌细胞中 BCL-2 mRNA 表达显着下调。紫杉醇和木犀草素联合使用对乳腺癌细胞具有协同作用,并显示出以下潜力:多种癌症的治疗方法。 鉴于这些有希望的结果,紫杉醇和木犀草素的组合可以开发成治疗各种癌症的有效治疗策略。未来的研究应包括体内研究,以进一步评估该组合的治疗潜力和安全性。版权所有 © 2024,Tamanna 等人。
According to reports on cancer incidence in 2020, breast cancer became the leading malignancy among women worldwide. This multistep disease involves genetic and environmental factors. Paclitaxel, a naturally occurring antimitotic substance, is a widely used chemotherapeutic drug for treating various human malignancies, including breast cancer. However, its major drawback is its extensive toxicity. This limitation can be mitigated through combination therapy with natural products like luteolin. Studies suggest that luteolin has anticancer properties, as it inhibits cancer cell growth and induces apoptosis in breast, lung, and colon cancers. This study aims to investigate the synergistic anticancer effects of combining luteolin and paclitaxel on breast cancer cells.Breast cancer cell line (MDA-MB-231) was utilized for this study. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was then conducted to check the cell viability. This was followed by a morphology study conducted under a phase contrast microscope. Morphological analysis revealed pronounced cell shrinkage and membrane blebbing, indicative of apoptosis when treated with the combination at their IC50 values. Gene expression results further confirmed the anticancer properties by showing significant downregulation of the B-cell lymphoma-2 (BCL-2) anti-apoptotic gene. These findings suggest that the luteolin-paclitaxel combination exerts a synergistic effect, enhancing anticancer activity in breast cancer cells. Reverse transcriptase polymerase chain reaction (RT-PCR) was done to analyze the genes involved in apoptosis. Finally, the data collected was statistically analyzed to confirm the reliability of the study.The combination of 1 μM/ml of paclitaxel and increasing concentrations of luteolin showed a great percentage of reduction in cell viability and the IC50 value of luteolin concentration was around 40 μM/ml. The morphology study revealed that the cancer cells showed shrinkage and blebbing on treatment with 40 μM/ml. At the same IC50 concentration, the combination of luteolin and paclitaxel resulted in a significant downregulation of BCL-2 mRNA expression in breast cancer cells compared to luteolin alone.The combination of paclitaxel and luteolin has a synergistic effect on breast cancer cells and shows potential as a treatment for various cancers. Given these promising results, the paclitaxel and luteolin combination could be developed into a potent therapeutic strategy for treating various cancers. Future research should include in vivo studies to further assess the therapeutic potential and safety profile of this combination.Copyright © 2024, Tamanna et al.