Title:Molecular Mechanism Analysis of the Effect of Hederagenin Combined with L-OHP on Chemosensitivity of AGS/L-OHP Based on Network
Pharmacology
Volume: 20
Author(s): Hongyue Tang, Chao Wang, Chenhao Xing, Guoxin liang, Chang Guo, Xin Liu, YanJie Li and Mingming Zhang*
Affiliation:
- Department of Clinical Medical Research Center, Hebei General Hospital, 050051, Shijiazhuang, Hebei, China
Keywords:
Gastric cancer, Hederagenin, drug resistance, chemosensitivity, oxaliplatin, signaling pathway.
Abstract: Aims and Objectives: This study aimed to evaluate the pharmacological mechanism
of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC)
through network pharmacology combined with experimental verification.
Material and Methods: Network pharmacology methods were used to screen potential targets
for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three
gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks
to predict core targets, and related pathways were predicted through GO and KEGG enrichment
analysis. The experimental results were verified by the in vitro experiments. HD was
applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp,
Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber
assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft
models transfected using AGS/L-OHP cells were also treated with HD in order to verify the
results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p-
Akt and p-PI3K genes, were also measured.
Results: KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly
by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched
genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells
jointly treated with HD and L-OHP, their activity, migration and invasion were significantly
lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p-
PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of
the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group
were the lowest compared to the HD group and L-OHP group.
Conclusion: Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP
by regulating the PI3K/Akt signaling pathway.
