Geng Beibei, Zhao Man, Wang Jun, Zhong Tian, Kang Chaoyan, Wang Zizhen, Ma Xin, Xia Ting
State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau, China.
Nat Prod Res. 2024 Dec 22:1-9. doi: 10.1080/14786419.2024.2440537.
T-cell acute lymphoblastic leukaemia (T-ALL) is a common childhood malignant tumour, which has poor prognosis and high recurrence rate. Ginsenoside Rh2 (GRh2), a bioactive ingredient of has significant anti-tumour effect. In this study, we found that gene expressions of Jurkat cells were significantly changed in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signalling pathways after 35 µm GRh2 treatment, involving in JUN, PIEN, AKT3 and MAPK8IP2. Target proteins including PI3K, AKT, ASK, caspase 8 and caspase 9 were bind tightly with GRh2 by molecular docking. Moreover, the protein expression ratios of p-PI3K/PI3K and p-AKT/AKT were significantly reduced, and the expression ratios of p-ASK1/ASK1, p-JNK/JNK and p-c-JUN/c-JUN, Bax/Bcl-2, and the levels of cleaved caspase 8, 9, 3 were increased significantly in GRh2-treated Jurkat cells. The results imply that GRh2 induced T-ALL apoptosis by activating the MAPK pathway and inhibiting the PI3K-AKT pathway.
T细胞急性淋巴细胞白血病（T-ALL）是一种常见的儿童恶性肿瘤，预后较差且复发率高。人参皂苷Rh2（GRh2）是[具体来源未明确]的一种生物活性成分，具有显著的抗肿瘤作用。在本研究中，我们发现35µm GRh2处理后，Jurkat细胞的基因表达在丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）信号通路中发生显著变化，涉及JUN、PIEN、AKT3和MAPK8IP2。通过分子对接发现，包括PI3K、AKT、ASK、半胱天冬酶8和半胱天冬酶9在内的靶蛋白与GRh2紧密结合。此外，在GRh2处理的Jurkat细胞中，p-PI3K/PI3K和p-AKT/AKT的蛋白表达比率显著降低，而p-ASK1/ASK1、p-JNK/JNK和p-c-JUN/c-JUN、Bax/Bcl-2的表达比率以及裂解的半胱天冬酶8、9、3的水平显著升高。结果表明，GRh2通过激活MAPK通路和抑制PI3K-AKT通路诱导T-ALL细胞凋亡。
