Explore the Potential Relationship between Local Anesthetics and Lung Adenocarcinoma under Hypoxia Condition

• Main Authors: CHAN SHUN-MING, 詹舜名
• Other Authors: WU ZHI-FU
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/d275cq

博士 === 國防醫學院 === 醫學科學研究所 === 106 === While anesthetics are often used on cancer patients during surgical procedures, their consequence on cancer progression remains to be clarified. In this study, we sought to investigate the mechanism of the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 and H1975 human lung adenocarcinoma cancer cells were processed with various local anesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. The cell barrier property was evaluated using an electric cell-substrate impedance sensing (ECIS) system. The epithelial-to-mesenchymal transition (EMT) of treated cells was analyzed by immunofluorescence staining. In vitro and in vivo cancer cell dissemination were investigated. Gene expression microarray and quantitative real-time PCR (qrt-PCR) assays were used to identify the genes responsible for levobupivacaine-mediated cancer cell dissemination. The results illustrated that only levobupivacaine induced EMT in the treated A549 cells and also caused the dissemination of cancer cells in vitro. In addition, after intravenous injection, levobupivacaine encouraged cancer cell dissemination in vivo (7/10 in the levobupivacaine treatment group compared to 1/10 in the control group). Gene expression microarray, qrt-PCR and immunoblotting revealed that after levobupivacaine treatment, the hypoxia-inducible factor (HIF)- 2α gene was upregulated in cancer cells. Our findings suggest that levobupivacaine may induce A549 lung cancer cell dissemination both in vitro and in vivo. More specifically, HIF-2α signaling possibly contributes to levobupivacaine-mediated A549 lung cancer cell spreading.