Keshavarz Fatemeh, Soltanshahi Mohsen, Khosravani Fatemeh, Bakhshiyan Farzaneh, Ghanbari Amir, Hassanzadeh Sajad, Amirpour Mozhgan, Ghalamfarsa Ghasem
Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):5157-5165. doi: 10.1007/s00210-024-02945-8. Epub 2024 Jan 19.
Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. Different factors, such as environmental and genetic factors and lifestyle, affect it. Owing to the presence of phenolic, alkaloid, antioxidant, and terpenoid compounds, herbal compounds can be effective in the treatment of various cancers. Thymol is a natural monoterpene phenol that is abundant in some plants and exerts several biological effects. The aim of this study was to investigate the apoptotic, anti-proliferative effect and EGFR gene expression under the influence of thymol-loaded nanoliposome in SW84 and SW111 cell lines derived from colorectal cancer.
The lipid thin-film hydration method was used to synthesize thymol-loaded liposomes, and their characterization was performed using TEM, DLS, and HPLC analyses. SW84 and SW1111 cells were treated with thymol- and thymol-loaded liposomes at different doses, the inhibition of cell proliferation was evaluated using an MTT assay, the rate of apoptosis induction was assessed using flow cytometry, and EGFR gene expression was measured using real-time PCR.
The nanoparticles produced were spherical, uniform, and 200 ± 10 nm in size. HPLC analysis showed that approximately 98% thymol was loaded into the nanoliposome. The results of the MTT assay showed that thymol and thymol-nanoliposomes decreased the proliferation of SW84 and SW1111 cells in a concentration-dependent manner. The IC50 of thymol and thymol-nanoliposomes were 18 and 14.2 µg/ml for the SW48 cell line (P = 0.04) and 10.5 and 6.4 µg/ml for the SW1116 cell line (P = 0.001). Thymol-nanoliposomes significantly inhibited the proliferation of cancer cells compared to free thymol. Flow cytometry showed an increase in the percentage of apoptotic cells, especially in the thymol-nanoliposome group in the treated cells. Real-time PCR results also showed that thymol and thymol-nanoliposome both caused a decrease in the expression of EGFR genes in both cell lines, but this effect of decreasing gene expression was significantly higher in the thymol-nanoliposome group.
Our results showed that thymol-nanoliposomes reduced proliferation, increased apoptosis, and decreased EGFR expression in colorectal cancer-derived cell lines.
结直肠癌（CRC）是全球最常见且致命的癌症之一。环境、遗传因素以及生活方式等不同因素都会对其产生影响。由于草药化合物中存在酚类、生物碱、抗氧化剂和萜类化合物，它们在治疗各种癌症方面可能具有疗效。百里香酚是一种天然单萜酚，在一些植物中含量丰富，并具有多种生物学效应。本研究的目的是探讨载有百里香酚的纳米脂质体对源自结直肠癌的SW84和SW111细胞系的凋亡、抗增殖作用以及表皮生长因子受体（EGFR）基因表达的影响。
采用脂质薄膜水化法合成载有百里香酚的脂质体，并通过透射电子显微镜（TEM）、动态光散射（DLS）和高效液相色谱（HPLC）分析对其进行表征。用不同剂量的百里香酚和载有百里香酚的脂质体处理SW84和SW1111细胞，采用MTT法评估细胞增殖抑制情况，通过流式细胞术评估凋亡诱导率，并使用实时定量聚合酶链反应（real-time PCR）测量EGFR基因表达。
所制备的纳米颗粒呈球形，大小均匀，直径为200±10纳米。HPLC分析表明，约98%的百里香酚被载入纳米脂质体。MTT法结果显示，百里香酚和载有百里香酚的纳米脂质体均以浓度依赖性方式降低SW84和SW1111细胞的增殖。对于SW48细胞系，百里香酚和载有百里香酚的纳米脂质体的半数抑制浓度（IC50）分别为18和14.2微克/毫升（P = 0.04）；对于SW1116细胞系，IC50分别为10.5和6.4微克/毫升（P = 0.001）。与游离百里香酚相比，载有百里香酚的纳米脂质体显著抑制癌细胞增殖。流式细胞术显示凋亡细胞百分比增加，尤其是在处理细胞中的载有百里香酚的纳米脂质体组。实时定量聚合酶链反应结果还表明,百里香酚和载有百里香酚的纳米脂质体均使两个细胞系中的EGFR基因表达降低，但载有百里香酚的纳米脂质体组中基因表达降低的效果更显著。
我们的结果表明，载有百里香酚的纳米脂质体可降低结直肠癌来源细胞系的增殖、增加凋亡并降低EGFR表达。
