1. Lidocaine inhibits the metastatic potential of ovarian cancer by blocking Na
- Author
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Chang, Liu, Ming, Yu, Yi, Li, Hao, Wang, Chuanya, Xu, Xiaoqing, Zhang, Min, Li, Hongyan, Guo, Daqing, Ma, and Xiangyang, Guo
- Subjects
endocrine system ,Epithelial-Mesenchymal Transition ,endocrine system diseases ,cisplatin ,Antineoplastic Agents ,NaV1.5 ,NAV1.5 Voltage-Gated Sodium Channel ,Cell Movement ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Animals ,Humans ,metastasis ,Neoplasm Metastasis ,Original Research ,Cancer Biology ,Ovarian Neoplasms ,Voltage-Gated Sodium Channel Blockers ,Lidocaine ,female genital diseases and pregnancy complications ,Mice, Inbred C57BL ,ovarian cancer ,Focal Adhesion Kinase 1 ,Female ,Paxillin ,Signal Transduction - Abstract
Lidocaine, one of the most commonly used local anesthetics during surgery, has been reported to suppress cancer cell growth via blocking voltage‐gated sodium channels (VGSCs). VGSC 1.5 (NaV1.5) is highly expressed in invasive cancers including ovarian cancer. This study aims to investigate whether lidocaine inhibits the malignancy of ovarian cancer through NaV1.5 blockage. Human ovarian cancer, its metastatic cancer and normal ovarian tissues were probed with anti‐NaV1.5 antibody in situ. Human ovarian cancer A2780 and SKOV3 cells were cultured and their growth, epithelial‐mesenchymal transition (EMT), migration, and invasion in the presence or absence of lidocaine together with underlying molecular mechanisms were assessed. Murine syngeneic ovarian cancer (ID8) model was also used to determine the chemotherapeutic efficiency of cisplatin in combination with lidocaine. The high level of NaV1.5 expression was found in human ovarian cancer and even higher in its metastatic cancer but not in normal ovarian tissues. Lidocaine decreased the growth, EMT, migration, and invasion of human ovarian cancer A2780 and SKOV3 cells. Lidocaine enhanced the chemotherapeutic efficiency of cisplatin in both ovarian cancer cell cultures and a murine ovarian metastatic model. Furthermore, a downregulation of NaV1.5 by siRNA transfection, or FAK inhibitor application, inhibited the malignant properties of SKOV3 cells through inactivating FAK/Paxillin signaling pathway. Our data may indicate that lidocaine suppresses the metastasis of ovarian cancer and sensitizes cisplatin through blocking NaV1.5‐mediated EMT and FAK/paxillin signaling pathway. The translational value of lidocaine local application as an ovarian cancer adjuvant treatment warrants further study., Local anesthetic lidocaine suppresses the metastasis of ovarian cancer and sensitizes cisplatin through blocking NaV1.5‐mediated EMT and FAK/paxillin signaling pathway. The translational value of lidocaine local application as an ovarian cancer adjuvant treatment warrants further study.
- Published
- 2020