Paris saponin VII enhanced the sensitivity of HepG2/ADR cells to ADR via modulation of PI3K/AKT/MAPK signaling pathway

Abstract

To find the effect of Paris saponin VII (PS VII)-mediated PI3K/AKT/MAPK signaling pathway on the sensitivity of ADR-resistant HepG2 cell (HepG2/ADR) cells to ADR.The proliferation inhibitory rates were detected by using MTT assay. Flow cytometry was employed to examine the intracellular accumulation of ADR. The expressions of drug-resistant genes (P-gp, MRP and BCRP) were detected by qRT-PCR, cell apoptosis by Annexin-V-FITC/PI staining, and the expressions of drug-resistance-related proteins, apoptosis-related proteins, and PI3K/AKT/MAPK pathway-related proteins were determined by Western blotting. HepG2/ADR and HepG2 cells treated with PS VII (0.88, 1.32, 1.98, and 2.97 μM) for 48 hours showed increased proliferation inhibitory rate in a dose-dependent manner. HepG2/ADR cells treated PS VII (0.88, 1.32, 1.98 μM) for 48 hours showed decreased IC50 of ADR. Compared with HepG2/ADR cells treated with ADR (5 nM), those treated with PS VII (≤1.98 μM) and ADR (5 nM) showed enhanced ADR accumulation, decreased drug-resistant gene expressions, increased cell apoptosis with unregulated Bax and cleaved caspase-3 and downregulated Bcl-2, as well as the inhibition of PI3K/AKT/MAPK pathway. Moreover, the combination of ADR (5 nM), PS VII (1.98 μM), and LY294002 (PI3K/AKT inhibitor, 20 μM)/SB203580 (P38 inhibitor, 20 μM) for 48 hours could further decreased the HepG2/ADR cell viability, but induced cell apoptosis, accompanying with the decreased expressions of drug-resistant genes. PS VII could downregulate the expressions of drug-resistance genes, increase intracellular accumulation of ADR, promote cell apoptosis, and enhance the sensitivity of HepG2/ADR cells to ADR via

Network Pharmacology-Based Exploration on the Intervention of Qinghao Biejia Decoction on the Inflammation-Carcinoma Transformation Process of Chronic Liver Disease via MAPK and PI3k/AKT Pathway

“…Some active components in TCM may have a role in HCC by strategically regulating the PI3K/AKT/MAPK pathway. For example, Paris saponin VII reverses the drug resistance of HCC HepG-2/ADR cells by inhibiting the PI3K/AKT/MAPK signaling pathway [66]. Verbasine inhibits proliferation, migration, invasion, and apoptosis of HCC cells through down-regulation of PI3K/AKT and p38 and ERK/MAPK pathways [67].…”

Bioactive secondary metabolites in Paris polyphylla Sm. and their biological activities: A review

“…Paris saponin VI showed anticancer activity toward the liver cancer line with IC 50 of 8.18 μM and 6.65 μM (Wang et al, 2019). Paris saponin VII inhibited the growth of human cervical cancer cells with an IC 50 of 2.62 AE 0.11 μM (Zhang et al, 2014), liver cancer cells with an IC 50 of 0.80-2.75 μM (Wang et al, 2019;Tang et al, 2019) and drug-resistant ovarian cancer cell lines (Yang et al, 2015a,b). Similarly, paris saponin H inhibited the growth of liver cancer cells with an IC 50 of 1.25 μM (Chen et al, 2019), diosgenin lung cancer cells with IC 50 of 149.75 AE 10.43 μM (Yan et al, 2009), pennogenins liver cancer cells with IC 50 of 9.7-13.5 μM (Zhu et al, 2011).…”

“…These compounds have also demonstrated suppression of carcinoma cell proliferation, cell autophagy and cell death occurs on the types of cancer cell lines and the compounds/drugs used via numerous routes based such as mitochondrial dysfunction (Lee et al, 2005;Cheung et al, 2005;Xiao et al, 2009;AlSawah et al, 2015;Wu et al, 2013;Zhang et al, 2014;Jiang et al, 2014aJiang et al, , 2014bZhao et al, 2015;Song et al, 2016;Yang et al, 2016;Tang et al, 2019;Wang et al, 2019), cell arrest at G2/M phase (Xiao et al, 2009;Jiang et al, 2014aJiang et al, , 2014bZhao et al, 2015;Lin et al, 2015;Song et al, 2016), cell arrest at G1-phase (Chen et al, 2018), cell arrest at G2/S-phase (Wang et al, 2019), ROS-oxidative stress pathway (Wang et al, 2019), mitogen-activated protein kinase (MAPK) pathways (Xiao et al, 2009;Chen et al, 2016), suppress pathological angiogenesis (Xiao et al, 2014;Yang et al, 2015a,b), suppress nuclear factor-κB (NF-κB) pathway (Yang et al, 2015a,b;Han et al, 2015;Chang et al, 2015;Chen et al, 2018;He et al, 2020), suppress vasculogenic mimicry (Xiao et al, 2018), suppress the CIP2A/AKT/m-TOR pathway (Feng et al, 2019), suppress PI3K/Akt pathway (He et al, 2020) and suppress ROS induced AKT/mTORC1 activity (Pang et al, 2019).…”