Department of Allied and Applied Medical Sciences, Division of anatomy biochemistry and genetics, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine.
Biomed Pharmacother. 2022 Dec;156:113885. doi: 10.1016/j.biopha.2022.113885. Epub 2022 Oct 18.
Gundelia (G.) tournefortii has antibacterial, anti-inflammatory, and hypolipemic effects. We evaluated the anticancer effect of G. tournefortii in an hepatocellular carcinoma (HCC) mouse model of an HCC cell line (Hep3B) injected into NOD.CB17-Prkdc-SCID/NCrHsD male mice. Tumorigenicity was assessed by tumor size, histology, serum α-fetoprotein (αFP), and glypican 3 (GPC3). HCC-related gene expression of the cell cycle (Cyclin-dependent kinase inhibitor 2A (CDNK2A)), proliferation (MKI67), and platelet-derived growth factor receptor α (PDGFA) were measured. HCC cell cycle alterations, apoptosis, and antioxidant markers in serum and liver following treatment with G. tournefortii were determined. Signaling pathways of liver p53 and phosphorylated PI3K, AKT, and mTOR were also evaluated. Results indicate a significant increase in tumor size in HCC animals associated with elevated αFP, GPC3, and MKI67. Tumor markers of p53 and phosphorylated AKT/PI3K/mTOR signaling pathway were diminished, with less proliferating cells and reduced PDGFRA gene expression following G. tournefortii infection. H&E staining showed a remarkable reduction in inflammatory lesions in HCC mice treated with G. tournefortii. This result was in line with a significant delay in the G2/M phase of HCC-primary hepatocytes by 1.39- to 2.4-fold and reduced HCC necrosis associated with inhibited CDNK2A gene expression. Antioxidant activity was significantly lower in the HCC mice than in the control group. Moreover, G. tournefortii inhibited the HCC formation of 3D MCTS spheroids. G. tournefortii treatment markedly restored antioxidant levels and displayed anticancer and antiproliferative effects and could be a promising cancer therapy.
千里光（G.）tournefortii 具有抗菌、抗炎和降血脂作用。我们评估了千里光在注射肝癌细胞系（Hep3B）的 NOD.CB17-Prkdc-SCID/NCrHsD 雄性小鼠肝癌（HCC）小鼠模型中的抗癌作用。通过肿瘤大小、组织学、血清 α-胎蛋白（αFP）和糖蛋白 3（GPC3）评估致瘤性。测量与细胞周期（细胞周期蛋白依赖性激酶抑制剂 2A（CDNK2A））、增殖（MKI67）和血小板衍生生长因子受体α（PDGFA）相关的 HCC 相关基因表达。测定用千里光治疗后血清和肝脏中 HCC 细胞周期改变、细胞凋亡和抗氧化标志物。还评估了肝脏 p53 和磷酸化 PI3K、AKT 和 mTOR 信号通路。结果表明，与升高的αFP、GPC3 和 MKI67 相关，HCC 动物的肿瘤体积显著增加。p53 和磷酸化 AKT/PI3K/mTOR 信号通路的肿瘤标志物减少，用千里光感染后增殖细胞减少，PDGFRA 基因表达降低。H&E 染色显示用千里光治疗的 HCC 小鼠的炎症病变明显减少。这一结果与 HCC 原代肝细胞 G2/M 期显著延迟 1.39-2.4 倍以及与抑制 CDNK2A 基因表达相关的 HCC 坏死减少一致。与对照组相比，HCC 小鼠的抗氧化活性明显降低。此外，千里光抑制 3D MCTS 球体的 HCC 形成。千里光治疗明显恢复抗氧化水平，表现出抗癌和抗增殖作用，可能是一种有前途的癌症治疗方法。
