| مستخلص: |
Objective We aimed to (i) compare the effects of renshen (ginseng) and huangqi (milkvetch root) on different cancer cells and (ii) elucidate the molecular mechanisms underlying the similarities and differences in their medicinal properties. Methods The effects of ginseng standard extract (RSE75) and milkvetch root standard extract (HQE75) on the proliferative activity of different cancer cells(Hep G2, H22, H1299, A549, EC109, and AKR) were determined by the CCK-8 assay. The effects of RSE75 and HQE75 on the mRNA expression levels of immune factors IL-6, TNF-α, and TGF-β and the balance between DNA methyltransferases (DNMTs) and TET2 in A549 cells were determined by RT-qPCR. The effects of RSE75 and HQE75 on the clonal formation rate, apoptosis, and the cell cycle of A549 cells were detected by a clonal formation assay, Annexin V-FITC/PI staining, and flow cytometry, respectively. The potential targets and pathways of RSE75 and HQE75 in the treatment of lung cancer were explored by RNA sequencing technology. Results Compared with the blank group, the survival rate of cancer cells in the RSE75 group was decreased, but there was no significant change in the HQE75 group. The mRNA expression levels of IL-6, TNF-α, and TGF-β were decreased in the RSE75 and HQE75 groups. RSE75 inhibited the clonal formation of A549 cells in a concentration-dependent manner, while HQE75 had no obvious inhibitory effect. Both RSE75 and HQE75 significantly induced apoptosis in A549 cells and blocked DNA replication in the G1/S phase. At the same concentration, RSE75 has a stronger effect on inducing apoptosis than HQE75. The mRNA expression level of DNMTs in the RSE75 group was decreased, the mRNA expression level of TET2 in the RSE75 group was increased, and the mRNA expression level of both DNMTs and TET2 was decreased in the HQE75 group. The RNA sequencing result showed that RSE75 and HQE75 had common targets, including CXCL8, CXCL1, ICAM1, and CCL2. The common pathways of action mainly included the IL-17 signaling pathway, the NF-κB signaling pathway, and the TNF signaling pathway, and most of them were involved in immune regulation. The main difference is that renshen can inhibit the proliferation of cancer cells through the HIF-1 signaling pathway through VEGFA, EGR1, and other targets, while huangqi can regulate amino acid metabolism and the NOD-like receptor signaling pathway through IL-6, TNF, and other targets. Conclusion Studies on the anti-cancer effects and the underlying molecular mechanisms have shown that renshen and huangqi have obvious immunomodulatory effects, but renshen also had significant inhibitory effects on cancer cell proliferation. Renshen could regulate the DNMTs/TET2 balance, while huangqi could inhibit the expression of DNMTs. This study elucidated the different properties of renshen and huangqi the molecular level and provides not only a scientific basis for clinical application of renshen and huangqi, which are both qi-tonifying medicinals, but also ideas for the study of the molecular mechanisms underlying the effects of other TCMs. [ABSTRACT FROM AUTHOR] |
