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

Yingqiu Yin; Junling Xie; Feng Peng; Liming Tan; Yun Xiao; Huiying Zheng; Lingzhi Yin; Huijing Situ; Shanqiang Zhang

doi:10.1016/j.heliyon.2023.e15805

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

Heliyon. 2023 Apr 27;9(5):e15805. doi: 10.1016/j.heliyon.2023.e15805. eCollection 2023 May.

Authors

Yingqiu Yin¹, Junling Xie¹, Feng Peng¹, Liming Tan², Yun Xiao¹, Huiying Zheng¹, Lingzhi Yin¹, Huijing Situ³, Shanqiang Zhang^{4

5}

Affiliations

¹ Respiratory Medical Department, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan City, Guangdong Province, China.
² Science and Education Department, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan City, Guangdong Province, China.
³ Department of Radiotherapy, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan City, Guangdong Province, China.
⁴ Department of Anatomy, Shantou University Medical College, Shantou City, Guangdong Province, China.
⁵ Medical Research Center, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan City, Guangdong Province, China.

Abstract

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 LC-related 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.

Keywords: CPT-11; EGFR; Lung cancer; MAPK pathway; Metastatic tumor model; Subcutaneous xenograft tumor model; Topoisomerase inhibitor.