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TWIK相关的酸敏感钾通道3（TASK-3）对麻醉药对卵巢癌细胞生长和转移的不同影响起作用。

The TWIK-related acid sensitive potassium 3 (TASK-3) channel contributes to the different effects of anesthetics on the growth and metastasis of ovarian cancer cells.

作者信息

Hu Zhiqiang, Jia Qi, Yao Shanglong, Chen Xiangdong

机构信息

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Heliyon. 2024 Jul 25;10(15):e34973. doi: 10.1016/j.heliyon.2024.e34973. eCollection 2024 Aug 15.

DOI:10.1016/j.heliyon.2024.e34973
PMID:39161826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11332837/
Abstract

Different anesthetics exert different effects on the long-term outcomes of various cancers. The TWIK-related acid sensitive potassium 3 (TASK-3) channel is an important target of anesthetics and is upregulated in various cancers. However, the role and underlying mechanism of TASK-3 channel in the effects of anesthetics on ovarian cancer remain unknown. Here, we tested whether the TASK-3 channel contributes to the effects of anesthetics on ovarian cancers. We found that the TASK-3 channel was overexpressed in human ovarian cancer and ovarian cancer cell lines. Clinically relevant concentrations of lidocaine, as a TASK-3 channel inhibitor, exert inhibitory effects on tumor growth and metastasis of ovarian cancer cells and , whereas the TASK-3 channel potent activator sevoflurane had protumor effects and propofol had no significant effects on tumor growth and metastasis of ovarian cancer. Knockdown of the TASK-3 channel by TASK-3 shRNA attenuated the effects of lidocaine and sevoflurane. Moreover, mitochondrial TASK-3 channel contributes to the effects of lidocaine and sevoflurane on the mitochondrial functions of ovarian cancer. Taken together, the TASK-3 channel, especially the mitochondrial TASK-3 (MitoTASK-3) channel, is a molecular substrate for the effects of lidocaine and sevoflurane on the tumor growth and metastasis of ovarian cancer.

摘要

不同的麻醉剂对各种癌症的长期预后产生不同的影响。TWIK相关酸性敏感钾通道3（TASK-3通道）是麻醉剂的重要靶点，在各种癌症中上调。然而，TASK-3通道在麻醉剂对卵巢癌影响中的作用及潜在机制仍不清楚。在此，我们测试了TASK-3通道是否参与麻醉剂对卵巢癌的影响。我们发现TASK-3通道在人卵巢癌及卵巢癌细胞系中过表达。作为TASK-3通道抑制剂，临床相关浓度的利多卡因对卵巢癌细胞的肿瘤生长和转移具有抑制作用，而TASK-3通道强效激活剂七氟醚具有促肿瘤作用，丙泊酚对卵巢癌的肿瘤生长和转移无显著影响。通过TASK-3 shRNA敲低TASK-3通道可减弱利多卡因和七氟醚的作用。此外，线粒体TASK-3通道参与利多卡因和七氟醚对卵巢癌线粒体功能的影响。综上所述，TASK-3通道，尤其是线粒体TASK-3（MitoTASK-3）通道，是利多卡因和七氟醚影响卵巢癌肿瘤生长和转移的分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/bfa395422754/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/80752821872d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/7d4959f479d1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/a7748214292a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/d3670a377a2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/50c47e83f09c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/d2625facfa1d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/2324616874ff/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/bfa395422754/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/80752821872d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/7d4959f479d1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/a7748214292a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/d3670a377a2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/50c47e83f09c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/d2625facfa1d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/2324616874ff/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9750/11332837/bfa395422754/gr8.jpg

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Cell Rep. 2023 Dec 26;42(12):113437. doi: 10.1016/j.celrep.2023.113437. Epub 2023 Nov 22.
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Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer.手术前肿瘤周围浸润局部麻醉对早期乳腺癌生存的影响。
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Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms.
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Cell Biol Toxicol. 2023 Aug;39(4):1395-1411. doi: 10.1007/s10565-022-09766-6. Epub 2022 Oct 8.
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