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Normobaric hyperoxia re-sensitizes paclitaxel-resistant lung cancer cells

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Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Chemoresistance is a substantial obstacle in cancer therapy. The microenvironment of solid tumor growth can be hypoxic, which promotes the survival, growth, and progression of cancer cells and reduces the effects of chemotherapy and radiotherapy. Hyperoxia treatment has potential to enhance cancer therapies.

Objective

We evaluated whether normobaric hyperoxia (NBO) therapy has an anticancer effect and can be a strategy for overcoming anticancer drug resistance. Human alveolar adenocarcinoma (A549) and paclitaxel (PTX)-resistant (A549/PR) cell lines were used. Cells were assessed after exposure to room air (RA) or NBO for 48 h with and without PTX application.

Results

NBO exposure inhibited cell viability, migration abilities, and proliferation in both cell lines. Chemo-resistant cell lines have shown variable viability upon NBO exposure. NBO exposure induced critical cytotoxicity and attenuated the characteristics of cancer in A549/PR cells. NBO induced a decline of chemoresistance in A549/PR cells when co-treated with PTX, consequently increasing cell death. In addition, NBO leads to intracellular reactive oxygen species and induced endoplasmic reticulum (ER) stress through the CCAAT/enhancer-binding protein homologous protein (CHOP) signaling pathway.

Conclusion

In summary, NBO increased cell death in lung cancer cells and promoted PTX re-sensitization in A549/PR cells through apoptosis and CHOP-mediated ER stress.

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Acknowledgements

This research was supported by grants from the Research Institute of Medical Science of The Catholic University of Korea, Eunpyeong St. Mary’s Hospital, and by the Catholic Medical Center Research Foundation in the program year of 2020.

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Authors and Affiliations

  1. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Jeonghyeon Im, Hee Young Kwon, In Kyoung Kim, Chang Dong Yeo, Sei Won Kim, Heayon Lee, Hye Seon Kang & Sang Haak Lee

  2. Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    In Kyoung Kim & Sang Haak Lee

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  1. Jeonghyeon Im
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Contributions

All the authors contributed to this study including designing research studies, conducting experiments, acquiring data, analyzing data, providing reagents, and writing the manuscript.

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Correspondence to Sang Haak Lee.

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The author Jeonghyeon Im, Hee Young Kwon, In Kyoung Kim, Chang Dong Yeo, Sei Won Kim, Heayon Lee, Hye Seon Kang, and Sang Haak Lee declare that he/she has no conflict of interest.

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Im, J., Kwon, H.Y., Kim, I.K. et al. Normobaric hyperoxia re-sensitizes paclitaxel-resistant lung cancer cells. Mol. Cell. Toxicol. 18, 539–548 (2022). https://doi.org/10.1007/s13273-022-00225-1

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