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Mesenchymal Stem Cells Carrying IFN-α and IFN-β Overexpression Genes Inhibit Non-Small Cell Lung Cancer via the JAK/STAT Pathway

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Abstract

IFN-α and IFN-β have been reported to have antitumor effects. This study explored the effect and molecular mechanism of IFN-α/IFN-β overexpressing mesenchymal stem cells (MSCs) in treatment of non-small cell lung cancer. Stable human umbilical cord-derived mesenchymal stem cells (hUCMSCs) overexpressing IFN-α and IFN-β (OE-MSCs) were obtained by lentiviral transfection. We first investigated the affinity of OE-MSCs for tumors, and then explored the effects of OE-MSCs on the viability and apoptosis of A549 and NCI-H2347 lung cancer cells. Next, in vivo experiments were performed in which OE-MSCs were injected into the tail veins of mice in a lung cancer tumor-bearing mouse model; after which, gene expression was detected by qRT-PCR, western blotting, and immunohistochemistry. Our results showed that the MSCs had stronger chemotaxis towards cancer cells. Moreover, the OE-MSCs produced and secreted IFN-α and IFN-β into the extracellular environment, and thereby reduced cancer cell viability and induced apoptosis. Knockdown of IFNAR1, the receptor for IFN-α and IFN-β, reduced the amount of damage done by OE-MSCs to lung cancer cells, and also inhibited the JAK/STAT pathway in lung cancer cells. Inhibition of JAK1 produced an effect similar to that of IFNAR1 knockdown. The antitumor effect of OE-MSCs was also confirmed by in vivo experiments, in which the weights and volumes of tumors in mice injected with OE-MSCs were significantly reduced. In conclusion, MSCs carrying IFN-α and IFN-β overexpression genes inhibited non-small cell lung cancer via the JAK/STAT pathway both in vivo and in vitro. Our results provide a theoretical basis for using stem cell therapy in treatment of non-small cell lung cancer.

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Funding

This research is supported by Natural Science Research Project of Anhui Educational Committee (KJ2021A0776, 2022AH051526, KJ2019A0366), Guangzhou Science and technology planning project (2023A03J0491).

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Authors and Affiliations

  1. Department of Geriatrics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

    Xiao Chen

  2. Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

    Kangwu Wang

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  1. Xiao Chen
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Correspondence to Kangwu Wang.

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This research is approved by the Ethics Committee of Bengbu Medical College (No. 2022-251; No. 2022-154).

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The authors declare that there is no relevant competing interest in this study.

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Chen, X., Wang, K. Mesenchymal Stem Cells Carrying IFN-α and IFN-β Overexpression Genes Inhibit Non-Small Cell Lung Cancer via the JAK/STAT Pathway. J Evol Biochem Phys 59, 1136–1149 (2023). https://doi.org/10.1134/S0022093023040105

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