Abstract
Adenocarcinoma, large cell carcinoma and squamous cell carcinoma are the most commonly diagnosed subtypes of non-small cell lung cancers (NSCLC). Numerous lung cancer cell types have exhibited electrotaxis under direct current electric fields (dcEF). Physiological electric fields (EF) play key roles in cancer cell migration. In this study, we investigated electrotaxis of NSCLC cells, including human large cell lung carcinoma NCI-H460 and human lung squamous cell carcinoma NCI-H520 cells. Non-cancerous MRC-5 lung fibroblasts were included as a control. After dcEF stimulation, NCI-H460 and NCI-H520 cells, which both exhibit epithelial-like morphology, migrated towards the cathode, while MRC-5 cells, which have fibroblast-like morphology, migrated towards the anode. The effect of doxycycline, a common antibiotic, on electrotaxis of MRC-5, NCI-H460 and NCI-H520 cells was examined. Doxycycline enhanced the tested cells’ motility but inhibited electrotaxis in the NSCLC cells without inhibiting non-cancerous MRC-5 cells. Based on our finding, further in-vivo studies could be devised to investigate the metastasis inhibition effect of doxycycline in an organism level.
Highlights
Over the past few decades, lung cancer has been the most common malignancy and the most common cause of cancer-related deaths globally[1]
Our data (Fig. 1a) showed that MRC-5 cells migrated towards the anode and H460 and H520 cells migrated towards the cathode under 300 mV/mm
Previous studies reported that human lung adenocarcinoma CL1-5 cells migrate towards the anode[9], whereas the human lung adenocarcinoma A549 cells migrate towards the cathode[15]
Summary
Over the past few decades, lung cancer has been the most common malignancy and the most common cause of cancer-related deaths globally[1]. A previous study demonstrated that EF in the tumour micro-environment could play a critical role in lung cancer metastasis by guiding cell migration[20]. Numerous studies have reported that doxycycline exhibits anti-tumour and pro-apoptotic activity. It decreases the tumour burden, Taoyuan, Taiwan. Several studies have reported that doxycycline inhibits cancer metastasis[28,29,30]. Literature reports have demonstrated doxycycline’s anti-metastasis effects, examining the role of doxycycline in NSCLC could help exploit its anti-cancer potential. We investigated the migration responses of human fetal lung fibroblast cell line MRC-5, human large cell lung carcinoma cell line NCI-H460 (H460) and human lung squamous cell carcinoma cell line NCI-H520 (H520) to external direct current electric fields (dcEFs). This work is a two-fold study on NSCLC migration, where we explore the influence of (1) EF and (2) doxycycline on the electrotaxis of MRC-5, H460 and H520 cells
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