Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model
Abstract The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39704-3 |
| _version_ | 1797752761236848640 |
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| author | Ji Hae Jun Jae-Kwang Shim Ju Eun Oh Kwang-Sub Kim Young-Lan Kwak Sarah Soh |
| author_facet | Ji Hae Jun Jae-Kwang Shim Ju Eun Oh Kwang-Sub Kim Young-Lan Kwak Sarah Soh |
| author_sort | Ji Hae Jun |
| collection | DOAJ |
| description | Abstract The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1β and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1β, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1β signaling-induced inflammation and enhancing NK cell activity. |
| first_indexed | 2024-03-12T17:08:11Z |
| format | Article |
| id | doaj.art-53a5b02a75d4431798546a666e812757 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T17:08:11Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-53a5b02a75d4431798546a666e8127572023-08-06T11:13:38ZengNature PortfolioScientific Reports2045-23222023-08-011311710.1038/s41598-023-39704-3Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft modelJi Hae Jun0Jae-Kwang Shim1Ju Eun Oh2Kwang-Sub Kim3Young-Lan Kwak4Sarah Soh5Anesthesia and Pain Research Institute, Yonsei University College of MedicineAnesthesia and Pain Research Institute, Yonsei University College of MedicineAnesthesia and Pain Research Institute, Yonsei University College of MedicineDepartment of Anesthesiology and Pain Medicine, Yonsei University College of MedicineAnesthesia and Pain Research Institute, Yonsei University College of MedicineAnesthesia and Pain Research Institute, Yonsei University College of MedicineAbstract The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1β and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1β, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1β signaling-induced inflammation and enhancing NK cell activity.https://doi.org/10.1038/s41598-023-39704-3 |
| spellingShingle | Ji Hae Jun Jae-Kwang Shim Ju Eun Oh Kwang-Sub Kim Young-Lan Kwak Sarah Soh Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model Scientific Reports |
| title | Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model |
| title_full | Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model |
| title_fullStr | Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model |
| title_full_unstemmed | Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model |
| title_short | Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model |
| title_sort | effects of dexmedetomidine on a549 non small cell lung cancer growth in a clinically relevant surgical xenograft model |
| url | https://doi.org/10.1038/s41598-023-39704-3 |
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