Dataset Information

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

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.

SUBMITTER: Yin Y

PROVIDER: S-EPMC10208938 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

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

Yin Yingqiu Y Xie Junling J Peng Feng F Tan Liming L Xiao Yun Y Zheng Huiying H Yin Lingzhi L Situ Huijing H Zhang Shanqiang S

Heliyon 20230427 5

<h4>Objective</h4>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.<h4>Methods</h4>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 prot ...[more]

PMID: 37251857

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Project description:Rationale: Müller cells play an essential role in maintaining the health of retinal photoreceptors. Dysfunction of stressed Müller cells often results in photoreceptor degeneration. However, how these cells communicate under stress and the signalling pathways involved remain unclear. In this study, we inhibited the MAPK (ERK1/2) signalling, mainly activated in Müller cells, evaluated the protective effects on the photoreceptors and further explored the signalling communication between stressed Müller cells and degenerating photoreceptors. Methods: We evaluated the changes of MAPK (ERK1/2) signalling and its downstream targets in human retinal explants treated with PD98059, a specific phosphorylated ERK1/2 inhibitor, by western blot and immunostaining. We further assessed photoreceptor degeneration by TUNEL staining and outer nuclear layer thickness. We also injected PD98059 into the eyes of mice exposed to photo-oxidative stress. We evaluated the protective effects on photoreceptor degeneration by optical coherence tomography (OCT) and electroretinography (ERG). The crosstalk between Müller cells and photoreceptors was further dissected based on the changes of transcription factors by RNA sequencing and protein profiles of multiple signalling pathways. Results: We found that MAPK (ERK1/2) signalling was mainly activated in Müller cells under stress, both ex vivo and in vivo. PD98059 inhibited the phosphorylation of ERK1/2, reduced expression of the gliotic marker glial fibrillary acidic protein (GFAP) in Müller cells and increased levels of the neuroprotective factor, interphotoreceptor retinoid-binding protein (IRBP) in photoreceptors. Inhibition of pERK1/2 also reduced retinal photo-oxidative damage in mice retinas assessed by OCT and ERG. We also identified that the JAK/STAT3 signalling pathway might mediate signalling transduction from Müller cells to photoreceptors. Conclusion: MAPK (ERK1/2) deactivation through chemical inhibition, mainly in stressed Müller cells, can alleviate gliosis in Müller cells and restore the expression of IRBP in photoreceptors, which appears to prevent retinal degeneration. Our findings suggested a new way to prevent photoreceptor degeneration by manipulating the stress response in Müller cells.

Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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