Oridonin inhibits the migration and epithelial‐to‐mesenchymal transition of small cell lung cancer cells by suppressing FAK‐ERK1/2 signalling pathway

Abstract

Small cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 μmol/L).Meanwhile, cell migration was suppressed by oridonin (5 and 10 μmol/L) that did not affect cell proliferation and apoptosis. The expression level of E-cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin β1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2.In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E-cadherin expression and reduced vimentin and phospho-FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial-to-mesenchymal transition (EMT) of SCLC cells by suppressing the FAK-ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti-SCLC with relative safety. K E Y W O R D Sfocal adhesion kinase, migration, oridonin, small cell lung cancer | 4481 XU et al.

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity

“…As documented in literature, utilization of oridonin increased the level of E-cadherin and ALP, reduced the vimentin, phospho-FAK levels, snail, slug, and LDH in human small cell lung cancer cell line H1688 with concentration of 2.5, 5, 10, 20, and 40 µM for 24 and 48 h in vitro. Of course, the author also confirmed the antilung cancer effect of oridonin in the model of BALB/c nude mice (Xu et al, 2020). Another study on the anti-lung cancer of oridonin proved that, oridonin sensitized cisplatin-induced apoptosis via AMPK/Akt/mTOR-dependent autophagosome accumulation in A549 Cells (Yang et al, 2019a).…”

“…However, several lines of evidence indicated that oridonin may exhibit adverse effects, even toxicity under specific circumstances, which sparked intense debate and concern about security of oridonin. As discussed above, it was discovered that oridonin showed antitumor activity on small cell lung cancer (SCLC), but at the same time, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment with oridonin (10 mg/kg) ( Xu et al, 2020 ). In addition, intervention of oridonin induced abnormalities in zebrafish, such as uninflated swim bladder and pericardial congestion at an EC 50 of 411.94 mg/L in vitro , as well as it also decreased the body length of zebrafish.…”

Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells

“…CIS is one of the first-line choices chemotherapeutic drugs for esophageal squamous cell carcinoma (ESCC), which shows the promising effect; however, it is a cell cycle nonspecific drug, has no clear target tissue and poses several adverse effects. On the other hand, ORI, a major diterpenoid component of leaf extracts from Rabdosia rubescens, has been demonstrated to be effective to a number of cancers [ 17 ], such as esophagus [ 18 ], leukemia [ 19 ], lung [ 20 ], pancreatic [ 21 ], prostate [ 22 ], breast [ 23 ] and colon[ 24 ] both in vivo / in vitro . In the current study, we report for the first time a synergistic antitumor effect of CIS and ORI on human ESCC cells, the main finding is that using CIS plus ORI has a selective synergistically effect to p53-mutant ESCC.…”

The Effect of Terpenoid Natural Chinese Medicine Molecular Compound on Lung Cancer Treatment

“…It has the ability to inhibit the proliferation of H1688 cells and induce their apoptosis under high-dose treatment (20 μ mol/L). At the same time, oridonin (5 and 10 μ mol/L) inhibits the FAK-ERK1/2 signaling pathway without affecting cell proliferation and apoptosis [ 69 ].…”