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Gamma linolenic acid suppresses hypoxia-induced proliferation and invasion of non-small cell lung cancer cells by inhibition of HIF1α

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Abstract

Background

The main therapies for cancer often results in many side effects and drug resistance. Gamma linolenic acid (GLA) is a kind of natural reagent with negligible cytotoxicity.

Objective

This work aims at detecting whether GLA possesses anti-cancer activity in NSCLC cells and elucidating the potential molecular mechanism.

Methods

Cytotoxicity of GLA was evaluated by MTT assay and soft agar colony formation method. Immunoblotting analysis examined the effect of GLA on protein expressions of cell proliferation markers (e.g., PCNA, Ki-67 and MCM2), pro-survival protein bcl-2, apoptosis-associated proteins (e.g., bax and cleaved caspase 3), HIF1α and VEGF. Wound healing assay and transwell invasion assay were performed to test the effect of GLA on hypoxia-induced cell migration and invasion. Cell transfection was used to overexpress HIF1α followed by the treatment of GLA to test the effect of HIF1α overexpression on the tumoricidal activity of GLA in NSCLC cell lines.

Results

MTT and soft agar colony formation tests showed that GLA dose-dependently suppressed cell proliferation in both Calu-1 and SK-MES-1 cell lines. Immunoblotting analysis demonstrated that GLA suppressed protein expressions of PCNA, Ki-67, MCM2 and bcl-2, while GLA induced bax and cleaved caspase 3 expressions. Wound healing assay and transwell invasion assay revealed that GLA was very effective on the inhibition of NSCLC cell migration and invasion. Immunoblotting analysis and cell transfection method indicated that GLA inhibited hypoxia-induced cell proliferation and invasion by suppressing HIF1α-VEGF pathway.

Conclusion

GLA suppresses hypoxia-induced proliferation and invasion of NSCLC cells by inhibition of HIF1α pathway in vitro.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Nutrition, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China

    Yan Wang, Jian Shi & Liya Gong

Authors
  1. Yan Wang
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  2. Jian Shi
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  3. Liya Gong
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Contributions

YW conceived and designed the experiments, JS analyzed and interpreted the results of the experiments, LYG performed the experiments.

Corresponding author

Correspondence to Yan Wang.

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Conflict of interest

Yan Wang, Jian Shi and Liya Gong declare that they have no conflict of interest.

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The animal use protocol listed below has been reviewed and approved by the Animal Ethical and Welfare Committee.

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Wang, Y., Shi, J. & Gong, L. Gamma linolenic acid suppresses hypoxia-induced proliferation and invasion of non-small cell lung cancer cells by inhibition of HIF1α. Genes Genom 42, 927–935 (2020). https://doi.org/10.1007/s13258-020-00961-5

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  • DOI: https://doi.org/10.1007/s13258-020-00961-5

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