Department of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Appl Biochem Biotechnol. 2022 Oct;194(10):4930-4945. doi: 10.1007/s12010-022-04000-9. Epub 2022 Jun 8.
The most prevalent malignancy among women is breast cancer. Phytochemicals and their derivatives are rapidly being recognized as possible cancer complementary therapies because they can modify signaling pathways that lead to cell cycle control or directly alter cell cycle regulatory molecules. The phytochemicals' poor bioavailability and short half-life make them unsuitable as anticancer drugs. Applying PLGA-PEG NPs improves their solubility and tolerance while also reducing drug adverse effects. According to the findings, combining anti-tumor phytochemicals can be more effective in regulating several signaling pathways linked to tumor cell development. The point of the study was to compare the anti-proliferative impacts of combined artemisinin and metformin on cell cycle arrest and expression of cyclin D1 and apoptotic genes (bcl-2, Bax, survivin, caspase-7, and caspase-3), and also hTERT genes in breast cancer cells. T-47D breast cancer cells were treated with different concentrations of metformin (MET) and artemisinin (ART) co-loaded in PLGA-PEG NPs and free form. The MTT test was applied to assess drug cytotoxicity in T47D cells. The cell cycle distribution was investigated using flow cytometry and the expression levels of cyclin D1, hTERT, Bax, bcl-2, caspase-3, and caspase-7, and survivin genes were then determined using real-time PCR. The findings of the MTT test and flow cytometry revealed that each state was cytotoxic to T47D cells in a time and dose-dependent pattern. Compared to various state of drugs (free and nano state, pure and combination state) Met-Art-PLGA/PEG NPs demonstrated the strongest anti-proliferative impact and considerably inhibited the development of T-47D cells; also, treatment with nano-formulated forms of Met-Art combination resulted in substantial downregulation of hTERT, Bcl-2, cyclin D1, survivin, and upregulation of caspase-3, caspase-7, and Bax, in the cells, as compared to the free forms, as indicated by real-time PCR findings. The findings suggested that combining an ART/MET-loaded PLGA-PEG NP-based therapy for breast cancer could significantly improve treatment effectiveness.
女性最常见的恶性肿瘤是乳腺癌。植物化学物质及其衍生物正迅速被认为是可能的癌症辅助治疗方法，因为它们可以改变导致细胞周期控制的信号通路，或直接改变细胞周期调节分子。植物化学物质的生物利用度差和半衰期短，使其不适合作为抗癌药物。应用 PLGA-PEG NPs 可以提高其溶解度和耐受性，同时降低药物的不良反应。研究结果表明，联合使用抗肿瘤植物化学物质可以更有效地调节与肿瘤细胞发育相关的几种信号通路。本研究的目的是比较联合使用青蒿素和二甲双胍对细胞周期阻滞和细胞周期蛋白 D1 及凋亡基因（bcl-2、Bax、survivin、caspase-7 和 caspase-3）和 hTERT 基因在乳腺癌细胞中的表达的抗增殖作用。用不同浓度的二甲双胍（MET）和青蒿素（ART）共同负载在 PLGA-PEG NPs 和游离形式中处理 T-47D 乳腺癌细胞。应用 MTT 试验评估 T47D 细胞中药物的细胞毒性。用流式细胞术检测细胞周期分布，然后用实时 PCR 测定细胞周期蛋白 D1、hTERT、Bax、bcl-2、caspase-3 和 caspase-7 和 survivin 基因的表达水平。MTT 试验和流式细胞术的结果表明，每种状态在时间和剂量依赖性模式下对 T47D 细胞均具有细胞毒性。与各种药物状态（游离态和纳米态、纯态和组合态）相比，Met-Art-PLGA/PEG NPs 表现出最强的抗增殖作用，显著抑制了 T-47D 细胞的发育；而且，与游离态相比，用纳米形式的 Met-Art 组合处理导致 hTERT、Bcl-2、cyclin D1、survivin 的显著下调，以及 caspase-3、caspase-7 和 Bax 的显著上调，这表明通过实时 PCR 检测到细胞中的基因表达。这些发现表明，联合使用基于 ART/MET 负载的 PLGA-PEG NP 的治疗方法可能显著提高乳腺癌的治疗效果。
