Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 inhibitor, MI‑2, attenuates non‑small cell lung cancer cell proliferation, migration and invasion, and promotes apoptosis by suppressing the JNK/c‑JUN pathway

Wu,Chunyan; Ge,Wei; Wu,Yun

doi:10.3892/ol.2024.14598

Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 inhibitor, MI‑2, attenuates non‑small cell lung cancer cell proliferation, migration and invasion, and promotes apoptosis by suppressing the JNK/c‑JUN pathway

Authors:
- Chunyan Wu
- Wei Ge
- Yun Wu
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Affiliations: Department of Oncology, Baotou Central Hospital, Baotou, Inner Mongolia Autonomous Region 014040, P.R. China
Published online on: July 30, 2024 https://doi.org/10.3892/ol.2024.14598
Article Number: 465

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Abstract

Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors are effective in attenuating the progression of several types of cancer. However, their role in lung cancer requires further investigation. Therefore, the present study aimed to explore the effect of the MALT1 inhibitor, MI‑2, on the behavior of non‑small cell lung cancer (NSCLC) cells and to uncover their possible underlying mechanism of action. The mRNA and protein expression levels of MALT1 were detected in the human normal lung epithelial cell line BEAS‑2B, and the NSCLC cell lines, NCI‑H1299, NCI‑H1650, HCC827, A549 and NCI‑H23. Subsequently, NCI‑H1650 and A549 cells were treated with MI‑2. Additionally, NCI‑H1650 and A549 cells were co‑treated with anisomycin, a c‑JUN N‑terminal kinase (JNK) pathway activator, with or without MI‑2. The results illustrated that the mRNA and protein expression levels of MALT1 were significantly increased in NCI‑H1299, NCI‑H1650, A549 and NCI‑H23 cells compared with those in BEAS‑2B cells. Treatment of NCI‑H1650 and A549 cells with MI‑2 for 72 h reduced the optical density value as determined using the Cell Counting Kit‑8 assay. Consistently, the 5‑ethynyl‑2'‑deoxyuridine assay also showed that proliferation was reduced in MI‑2‑treated NSCLC cells. In addition, MI‑2 downregulated B‑cell lymphoma 2 (BCL2), and enhanced BCL2‑associated X‑protein expression and apoptotic rate in NCI‑H1650 and A549 cells. These findings indicated that MI‑2 could inhibit NCI‑H1650 and A549 cell proliferation and promote apoptosis. Furthermore, treatment of cells with MI‑2 only attenuated the migration and invasion of NCI‑H1650 cells. Notably, MI‑2 decreased the expression levels of phosphorylated (p)‑JNK and p‑c‑JUN in NCI‑H1650 and A549 cells, thus suggesting that MI‑2 could suppress the JNK/c‑JUN signaling pathway. However, NSCLC cell co‑treatment with anisomycin (JNK pathway activator) reversed the effect of MI‑2 on the proliferation, apoptosis and activation of the JNK/c‑JUN pathway in NCI‑H1650 and A549 cells. In conclusion, the present study demonstrated that the MALT1 inhibitor, MI‑2, could suppress NSCLC cell proliferation, migration and invasion, and induce apoptosis via inactivating the JNK/c‑JUN pathway.

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