The topoisomerase inhibitor CPT-11 prevents the growth and metastasis of lung cancer cells in nude mice by inhibiting EGFR/MAPK signaling pathway

Objective: The topoisomerase inhibitor CPT-11 has been applied in treatment of multiple cancer types. Here, we probed into the possible mechanism of CPT-11 in affecting growth and metastasis of lung cancer (LC) cells, with involvement of the EGFR/MAPK pathway.Methods: The target protein of CPT-11 was screened through bioinformatics analysis, and the LCrelated microarray datasets GSE29249, GSE32863 and GSE44077 were obtained for differential analysis for identifying the target protein. A subcutaneous xenograft tumor model and a metastatic tumor model were constructed in nude mice for in vivo mechanism verification of the regulatory role of CPT-11 in LC through modulation of EGRF/MAPK pathway.Results: Bioinformatics analysis showed that EGFR was the target protein of CPT-11. In vivo animal experiments confirmed that CPT-11 enhanced LC cell growth and metastasis in nude mice. CPT-11 could inhibit activation of EGFR/MAPK pathway. EGFR promoted LC cell growth and metastasis in nude mice through activation of the MAPK pathway.Conclusion: The topoisomerase inhibitor CPT-11 may prevent LC growth and metastasis by inhibiting activation of EGFR/MAPK pathway.

Automated summary

This study investigated the mechanism by which CPT-11 affects the growth and metastasis of lung cancer cells through the EGFR/MAPK pathway. Bioinformatics analysis identified EGFR as the target protein of CPT-11, and in vivo experiments confirmed that CPT-11 enhances lung cancer cell growth and metastasis by inhibiting the activation of the EGFR/MAPK pathway. Furthermore, it was found that EGFR promotes lung cancer cell growth and metastasis via the activation of the MAPK pathway.