Oridonin suppresses gastric cancer SGC‐7901 cell proliferation by targeting the TNF‐alpha/androgen receptor/TGF‐beta signalling pathway axis

Abstract

Statistics provided by GLOBOCAN list gastric cancer as the sixth most common, with a mortality ranking of third highest for the year 2020. In China, a herb called Rabdosia rubescens (Hemsl.) H.Hara, has been used by local residents for the treatment of digestive tract cancer for hundreds of years. Oridonin, the main ingredient of the herb, has a curative effect for gastric cancer, but the mechanism has not been previously clarified. This study mainly aimed to investigate the role of TNF‐alpha/Androgen receptor/TGF‐beta signalling pathway axis in mediating the proliferation inhibition of oridonin on gastric cancer SGC‐7901 cells. MTT assay, cell morphology observation assay and fluorescence assay were adopted to study the efficacy of oridonin on cell proliferation. The network pharmacology was used to predict the pathway axis regulated by oridonin. Western blot assay was adopted to verify the TNF‐α/Androgen receptor/TGF‐β signalling pathway axis regulation on gastric cancer by oridonin. The results showed Oridonin could inhibit the proliferation of gastric cancer cells, change cell morphology and cause cell nuclear fragmentation. A total of 11signaling pathways were annotated by the network pharmacology, among them, Tumour necrosis factor alpha (TNF‐α) signalling pathway, androgen receptor (AR) signalling pathway and transforming growth factor (TGF‐β) signalling pathway account for the largest proportion. Oridonin can regulate the protein expression of the three signalling pathways, which is consistent with the results predicted by network pharmacology. These findings indicated that oridonin can inhibit the proliferation of gastric cancer SGC‐7901 cells by regulating the TNF‐α /AR /TGF‐β signalling pathway axis.

Salidroside inhibited the proliferation of gastric cancer cells through up-regulating tumor suppressor miR-1343-3p and down-regulating MAP3K6/MMP24 signal molecules

“…This process is mainly depended on extracellular matrix metalloproteinases (MMPs). 34 , 35 Overexpressed MMPs often degrade basement membrane and ECM, then promote tumor angiogenesis and invasion. 36 , 37 MMP24 is a subfamily of matrix metalloproteinases.…”

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy – A comprehensive review

“…ORI may help inhibit the proliferation and fibrogenesis of hepatic stellate cells as it stimulates cell cycle arrest and cancerous cell apoptosis through p53-p21 pathways and does not cause toxicity in hepatocytes (Bohanon et al, 2014). genes can also be used as prognostic biomarkers (Gao et al, 2021;Gao et al, 2023).…”

“…The liver cancer survival rate was linked to ESR1, SPP1, and FOSB gene expression. Study reported that AURKA, SPP1, NUSAP1, UBE2C, TOP2A, AFP, PTTG1, GMNN, RRM2, CXCL12, SPARCL1, FOS, SOCS3, DCN, PCK1, and FOSB can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can also be used as prognostic biomarkers (Gao et al., 2021 ; Gao et al., 2023 ).…”

“…In ORI‐treated HGC‐27 cell line, differential expression of CytC, caspase‐3, and apoptosis protease‐activating factor‐1 is associated with the apoptosis (Sun et al., 2012 ). ORI may inhibit SGC‐7901 gastric cancer cells proliferation at IC 50 15.6 via modulating the TNF‐α/AR/TGF‐β signaling pathway axis (Gao et al., 2023 ). It also induces G2/M‐phase cell cycle arrest by decreasing the expression of cyclinB1 and CDK1 proteins (Gao et al., 2014 ).…”