Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Asian Pac J Cancer Prev. 2022 Dec 1;23(12):4063-4072. doi: 10.31557/APJCP.2022.23.12.4063.
The incidence of breast cancer continues to rise despite decades of laboratory, epidemiological and clinical research. Breast cancer is still the leading cause of cancer death in women. Cyclin D1 is one of the most important oncoproteins associated with cancer cell proliferation and is overexpressed in more than 50% of cases. Curcumin and chrysin are plant-derived components that are believed to assist in inhibiting the viability of breast cancer cells. These agents are involved in cancer cells' growth and reducing cyclin D1 expression. In this study, the hypothesis of combining curcumin and chrysin is applied to analyze the potential synergistic effect in inhibiting cancer cell proliferation and down-regulation of cyclin D1. Furthermore, applying PLGA-PEG NPs could improve the bioavailability of free curcumin and chrysin components and at the same time increases the anti-cancer potential of this compound.
PLGA-PEG NPs were synthesized via the ring-opening polymerization technique and characterized with FT-IR and FE-SEM for chemical structure and morphological characteristics, respectively. Next, curcumin and chrysin were loaded in PLGA-PEG NPs and MTT assay was performed to assess the cytotoxic effect of these agents. T-47D cells were treated with appropriate concentrations of these agents and cyclin D1 expression level was evaluated by real-time PCR.
The obtained results from FT-IR and FE-SEM techniques illustrated that curcumin and chrysin were efficiently encapsulated into PLGA-PEG NPs. Curcumin, chrysin, and curcumin-chrysin in free and nano-encapsulated forms exhibited an anti-cancer effect on T-47D cells in a time- and dose-dependent manner, especially in a combination of free and encapsulated forms demonstrated synergistic anti-cancer effects. Compared to free form, Nano-curcumin, Nano-chrysin, and Nano-combination remarkably down-regulated cyclin D1 gene expression. (p-value < 0.05).
Our results revealed that the curcumin-chrysin combination has a synergistic effect and the encapsulated form of this nano-component has more inhibition on cyclin D1 expression.
.
尽管经过了几十年的实验室、流行病学和临床研究，乳腺癌的发病率仍在持续上升。乳腺癌仍然是女性癌症死亡的主要原因。细胞周期蛋白 D1 是与癌细胞增殖最重要的癌蛋白之一，超过 50%的病例中过度表达。姜黄素和白杨素是植物衍生的成分，据信有助于抑制乳腺癌细胞的活力。这些药物参与癌细胞的生长和降低细胞周期蛋白 D1 的表达。在这项研究中，应用姜黄素和白杨素联合的假设来分析抑制癌细胞增殖和下调细胞周期蛋白 D1 的潜在协同作用。此外，应用 PLGA-PEG NPs 可以提高游离姜黄素和白杨素成分的生物利用度，同时增加该化合物的抗癌潜力。
通过开环聚合技术合成 PLGA-PEG NPs，并分别通过傅里叶变换红外光谱（FT-IR）和场发射扫描电子显微镜（FE-SEM）对其化学结构和形态特征进行表征。接下来，将姜黄素和白杨素载入 PLGA-PEG NPs 中，并通过 MTT 测定法评估这些药物的细胞毒性作用。用适当浓度的这些药物处理 T-47D 细胞，并通过实时 PCR 评估细胞周期蛋白 D1 的表达水平。
FT-IR 和 FE-SEM 技术获得的结果表明，姜黄素和白杨素被有效地包封在 PLGA-PEG NPs 中。游离和纳米包封形式的姜黄素、白杨素和姜黄素-白杨素在 T-47D 细胞中表现出时间和剂量依赖性的抗癌作用，尤其是游离和包封形式的组合表现出协同抗癌作用。与游离形式相比，纳米姜黄素、纳米白杨素和纳米组合显著下调细胞周期蛋白 D1 基因表达。（p 值<0.05）。
我们的结果表明，姜黄素-白杨素联合具有协同作用，这种纳米成分的包封形式对细胞周期蛋白 D1 表达的抑制作用更强。
