Department of Chemotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China; Department of Oncology, Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang, 222002, China.
Phase I Clinical Trial Center, Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang, 222002, China.
Carbohydr Res. 2024 Nov;545:109296. doi: 10.1016/j.carres.2024.109296. Epub 2024 Oct 23.
Bile acids have been known to play significant roles at certain physiological levels in gastrointestinal metabolism. Yet, they are known to be carcinogenic and aid in tumor progression in most cases, although the roles remain uncertain. Hence, we tested the cytotoxic potential of cholic acid (CA) loaded chitosan nanoparticles (CNPs) on Hep3B cells. The physicochemical properties of the CNPs synthesized with CA load (CA-CNPs) were determined using standard techniques such as ultraviolet-visible spectrophotometry (UV-Vis), fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The characteristic peak for chitosan nanoparticles were observed for plain CNPs (pCNPs) and CA-CNPs at around 300 nm as per UV-Vis analysis. FTIR analysis indicated the possible trapping of CA onto CNPs as certain peaks were retained and some peaks were shifted. XRD analysis determined that the peaks representing CA and pCNPs were collectively obtained in CA-CNPs. As per DLS analysis, the particle size, PDI and ζ-potential of the CA-CNPs were 259 nm, 0.284 and 30.4 mV. Further, the CA-CNPs were non-cytotoxic on Hep3B cells at the maximum tested concentration of 500 μg/mL. The viability at 500 μg/mL of CA-CNPs was two-fold higher than 500 μg/mL of pCNPs. Also, the pCNPs were not hemolytic and therefore could not have played a role in the increase of viability after treatment with CA-CNPs, which indicates that CA posed a major role in increased viability of Hep3B cells. As per quantitative PCR (qPCR), the upregulated gene expressions of PI3K, Akt, mTORC2, cMyc, Fibronectin, hVPS34, Slug and ZEB1 and the downregulated expression of the tumor suppressor PTEN indicates that PI3K/Akt/mTOR pathway mediated the induction of epithelial-to-mesenchymal transition (EMT) in response to CA-CNPs treatment on Hep3B cells.
胆汁酸在胃肠道代谢的某些生理水平上起着重要作用。然而，它们在大多数情况下被认为是致癌的，并有助于肿瘤的进展，尽管其作用仍不确定。因此，我们测试了载胆酸（CA）壳聚糖纳米粒（CNPs）对 Hep3B 细胞的细胞毒性。用标准技术如紫外可见分光光度法（UV-Vis）、傅里叶变换红外光谱（FTIR）、X 射线衍射（XRD）、动态光散射（DLS）和透射电子显微镜（TEM）测定合成的载 CA 的 CNPs（CA-CNPs）的物理化学性质。根据 UV-Vis 分析，壳聚糖纳米粒的特征峰出现在普通 CNPs（pCNPs）和 CA-CNPs 左右 300nm。FTIR 分析表明 CA 可能被捕获到 CNPs 上，因为某些峰被保留，而某些峰被移动。XRD 分析表明，代表 CA 和 pCNPs 的峰在 CA-CNPs 中共同获得。根据 DLS 分析，CA-CNPs 的粒径、PDI 和 ζ-电位分别为 259nm、0.284 和 30.4mV。此外，CA-CNPs 在 500μg/ml 的最大测试浓度下对 Hep3B 细胞无细胞毒性。CA-CNPs 在 500μg/ml 时的活力比 500μg/ml 的 pCNPs 高两倍。此外，pCNPs 没有溶血作用，因此在用 CA-CNPs 处理后不会在活力增加中起作用，这表明 CA 在 Hep3B 细胞活力增加中起主要作用。根据定量 PCR（qPCR），PI3K、Akt、mTORC2、cMyc、纤维连接蛋白、hVPS34、Slug 和 ZEB1 的上调基因表达以及肿瘤抑制因子 PTEN 的下调表达表明，PI3K/Akt/mTOR 途径介导了 CA-CNPs 处理 Hep3B 细胞后上皮-间质转化（EMT）的诱导。
