Topotecan inhibits metastasis of non-small cell lung cancer by regulating epithelial-mesenchymal transition

Abstract

Lung cancer is a malignant disease with a high mortality rate and a poor prognosis, which is easy to metastasis and recurrence. Topotecan (TPT), an inhibitor of topoisomerase I (Topo I), is mainly used to treat metastatic small cell lung cancer, and it has shown effective treatment for non-small cell lung cancer (NSCLC). However, the inhibitory effect and mechanism of TPT on NSCLC have not been described. In this study, we examined the effect of TPT on the proliferation of three types of NSCLC (H1299, H1975 and HCC827 ​cells) by MTT and colony formation assays. The migration capacity of lung cancer cells treated with TPT was detected by wound healing assay. We also tested the cell apoptosis induced by TPT using flow cytometry and the related proteins by Western blot. TPT treatment inhibited the proliferation of lung cancer cells with IC50 values of 12.67 ​± ​0.44 ​μM, 0.44 ​± ​0.083 ​μM and 2.89 ​± ​0.46 ​μM for H1299, H1975 and HCC827 ​cells, respectively. TPT promoted cell apoptosis by upregulating the expression of Bax and downregulating the expression of Bcl-xL and Bcl-2. Topotecan suppressed the metastatic phenotype of epithelial mesenchymal transition (EMT) in lung cancer cells by regulating E-cadherin, N-cadherin, vimentin and transcription factors Snail, MMP-2 and MMP-9. Our study found that TPT could inhibit the proliferation and migration of NSCLC by inducing cell apoptosis and regulating EMT. It was provided further favorable evidence for TPT in the treatment of patients with metastatic NSCLC.

Keywords

• Topotecan
• Non-small cell lung cancer
• EMT
• Cell apoptosis