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用于乳腺癌治疗的蝎毒功能化槲皮素磷脂体:体外响应面优化及对MCF-7细胞的抗癌活性

Scorpion Venom-Functionalized Quercetin Phytosomes for Breast Cancer Management: In Vitro Response Surface Optimization and Anticancer Activity against MCF-7 Cells.

作者信息

Alhakamy Nabil A, Fahmy Usama A, Eldin Shaimaa M Badr, Ahmed Osama A A, Aldawsari Hibah M, Okbazghi Solomon Z, Alfaleh Mohamed A, Abdulaal Wesam H, Alamoudi Abdulmohsin J, Mady Fatma M

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Polymers (Basel). 2021 Dec 27;14(1):93. doi: 10.3390/polym14010093.

Abstract

Breast cancer is a dangerous type of cancer in women. Quercetin (QRT), a naturally occurring flavonoid, has wide biological effects including antioxidant, anticarcinogenic, anti-inflammatory, antiallergic, and antiviral activities. The anticancer activity is considered the most valuable effect of QRT against several types of cancer, including prostate, liver, lung, colon, and breast cancer. Scorpion venom peptides (SV) has been found to induce apoptosis and aggravate cancer cells, making it a promising anticancer agent. QRT, SV, and Phospholipon 90H (PL) were incorporated in a nano-based delivery platform to assess QRT's cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human breast cancer cells MCF-7. Several nanovesicles were prepared and optimized, using four-factor Box-Behnken, in an experimental design. The optimized phytosomes showed vesicle size and zeta potential values of 116.9 nm and 31.5 mV, respectively. The IC50 values revealed that MCF-7 cells were significantly more sensitive to the optimized QRT formula than the plain formula and raw QRT. Cell cycle analysis revealed that optimized QRT formula treatment resulted in significant cell cycle arrest at the S phase. The results also indicated that treatment with QRT formula significantly increased caspase-9, Bax, Bcl-2, and p53 mRNA expression, compared with the plain formula and QRT. In terms of the inflammatory markers, the QRT formula significantly reduced the activity of TNF-α and NF-κB, in comparison with the plain formula and QRT only. Overall, the findings from the study proved that a QRT formulation could be a promising therapeutic approach for the treatment of breast cancer.

摘要

乳腺癌是女性中一种危险的癌症类型。槲皮素(QRT)是一种天然存在的类黄酮,具有广泛的生物学效应,包括抗氧化、抗癌、抗炎、抗过敏和抗病毒活性。抗癌活性被认为是QRT对多种癌症(包括前列腺癌、肝癌、肺癌、结肠癌和乳腺癌)最有价值的作用。蝎毒肽(SV)已被发现可诱导癌细胞凋亡并使其恶化,使其成为一种有前景的抗癌剂。将QRT、SV和磷脂90H(PL)整合到一个基于纳米的递送平台中,以评估QRT对源自人乳腺癌细胞MCF-7的肺癌细胞系的细胞摄取和抗增殖功效。在实验设计中,使用四因素Box-Behnken法制备并优化了几种纳米囊泡。优化后的植物脂质体的囊泡大小和zeta电位值分别为116.9 nm和31.5 mV。IC50值显示,MCF-7细胞对优化后的QRT配方比普通配方和未加工的QRT更敏感。细胞周期分析表明,优化后的QRT配方处理导致细胞在S期显著停滞。结果还表明,与普通配方和QRT相比,用QRT配方处理显著增加了caspase-9、Bax、Bcl-2和p53 mRNA的表达。在炎症标志物方面,与普通配方和仅QRT相比,QRT配方显著降低了TNF-α和NF-κB的活性。总体而言,该研究结果证明,QRT制剂可能是一种有前景的乳腺癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43f7/8747200/f5f94695b44f/polymers-14-00093-g001.jpg

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