Triptolide inhibits epithelial ‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells.

Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells. Oncol Rep. 2020 Mar 10;: Authors: Li F, Cui H, Jin X, Gong X, Wang W, Wang J Abstract The epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), gefitinib, is used widely to treat non‑small cell lung cancer (NSCLC) with EGFR‑activating mutations. Unfortunately, the acquired drug resistance promoted by epithelial‑mesenchymal transition (EMT) markedly limits the clinical effects and remains a major barrier to a cure. Our previous isobaric tags for relative and absolute quantitation‑based proteomics analysis revealed that the E‑cadherin protein level was markedly upregulated by triptolide (TP). The present study aimed to determine whether TP reverses the gefitinib resistance of human lung cancer cells by regulating EMT. It was revealed that TP combined with gefitinib synergistically inhibited the migration and invasion of lung adenocarcinoma cell line A549; the combination treatment had a significantly better outcome than that of TP and gefitinib alone. Moreover, TP effectively increased the sensitivity of drug resistant A549 cells to gefitinib by upregulating E‑cadherin protein expression and downregulating the MMP9, SNAIL, and vimentin expression levels. The dysregulated E‑cadherin expression of gefitinib‑sensitive cells induced gefitinib resistance, which could be overcome by TP...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research