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MFN2 Protein Regulates Cisplatin Sensitivity in Non-Small Cell Lung Cancer by Regulating Mitochondrial Autophagy

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Pharmaceutical Chemistry Journal Aims and scope

This work was aimed to explore the mechanism of Mfn2 protein dependent cisplatin sensitivity in non-small cell lung cancer (NSCLC) by regulating mitochondrial autophagy (MA) in several common NSCLC cell lines (H1299, h1650, H460, A549), A549/CDDP cisplatin-resistant cell lines, and human bronchial epithelioid (HBE) and nuli-1 cells. In comparison to nuli-1 and HBE cells, down-regulated Mfn2 expression in H1299, h1650, H460, A549 and A549/CDDP cells (P < 0.05) was observed. In addition, the expression of Mfn2 in A549/CDDP resistant strain was further down-regulated (P < 0.05) as compared with A549 parent strain. The pc-mfn2/A549 cells showed decreased proliferation and colony forming ability compared with pc-dna3.1/A549 (P < 0.05). The invasion and migration ability of pc-mfn2/A549 cells were significantly decreased (P < 0.05) as compared with pc-dna3.1/A549 cells. The Mfn2 knockout could reverse the inhibition of invasion and migration ability of A549 cells, and stable overexpression of Mfn2 inhibited the migration and invasion ability of A549 cells. Thus, Mfn2 regulates the proliferation, migration, invasion and sensitivity to cisplatin of NSCLC cells by regulating MA. It is suggested that Mfn2 can be used as a target for the treatment of cisplatin resistance in patients with NSCLC.

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Authors and Affiliations

  1. Department of Palliative Care, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China

    Hao Liu

  2. Department of Oncology, The First People’s Hospital of Kashgar, Kashi, 844000, Xinjiang Uygur Autonomous Region, China

    Chaoqun Wu & Talaiguli Xirenbaike

  3. Department of Anesthesiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang Uygur Autonomous Region, China

    Jiaqi Wei

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  1. Hao Liu
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  2. Chaoqun Wu
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  4. Talaiguli Xirenbaike
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Correspondence to Jiaqi Wei.

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Hao Liu and Chaoqun Wu contributed equally to this work and should be considered as co-first authors.

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Liu, H., Wu, C., Wei, J. et al. MFN2 Protein Regulates Cisplatin Sensitivity in Non-Small Cell Lung Cancer by Regulating Mitochondrial Autophagy. Pharm Chem J 57, 186–195 (2023). https://doi.org/10.1007/s11094-023-02866-5

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  • DOI: https://doi.org/10.1007/s11094-023-02866-5

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