Triptolide suppresses the growth and metastasis of non-small cell lung cancer by inhibiting β-catenin-mediated epithelial–mesenchymal transition

Abstract

Non-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial–mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed β-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of β-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of β-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

3D Collagen-Nanocellulose Matrices Model the Tumour Microenvironment of Pancreatic Cancer

“…In a step-wise strategy, we first assessed the effects of triptolide and gemcitabine combined with paclitaxel in PDAC cell monocultures grown in different hydrogels and found that triptolide was effective against MIA PaCa-2 cells but not PANC-1 cells. These differential responses may be explained by the anti-proliferative effects of triptolide on mesenchymal-like cells and an epithelial-mesenchymal transition ( 58 ). In contrast, gemcitabine and paclitaxel treatment exhibited lower efficacy in the PDAC cell monocultures, in particular MIA PaCa-2 cells, in the stiffer collagen-nanocellulose matrices compared to the soft collagen matrix.…”

A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer

“…Studies have shown that triptolide can regulate EMT in cancer progression by inhibiting the Wnt/β-catenin pathway, thus inhibiting the migration and invasion of tumor tissues ( Liu et al, 2015 ; Basu et al, 2018 ). Deng et al (2021) found that after triptolide treatment, the expression of the epithelial marker E-cadherin in NCI-H1299 cells was significantly increased, while the expressions of mesenchymal markers ZEB1, vimentin, and slug were decreased, and the expression of β-catenin was also inhibited. The researchers overexpressed and knocked out genes in NCI-H1299 and NCI-H460 cells, respectively, and β-catenin confirmed that inhibition of EMT is mediated by β-catenin.…”

Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

“…Diverse cellular events, including apoptosis, cellular senescence, and EMT, are influenced by triptolide [ 207 , 208 , 209 ], connoting its therapeutic benefit against cancer. Further, triptolide can attain its anti-pancreatic cancer activity via imposing limits on HIF-1α expression in vitro and in vivo [ 184 ].…”