Doxycycline inhibits electric field-induced migration of non-small cell lung cancer (NSCLC) cells

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.

Structure, function, and evolution of Gga -AvBD11, the archetype of the structural avian-double-β-defensin family

“…To explore the potential role of Gga-AvBD11 in regulating embryonic development and the expansion of the yolk sac membrane, we used National Cancer Institute (NCI)-H460 human cells derived from a human non-small-cell lung carcinoma. The use of this human cell line is motivated by the very limited availability of chicken cell lines with high proliferative and invasive capacities, and by the fact that the NCI-H460 cell line exhibiting high invasive capacities and an epithelium-like morphology is commonly used to assess pro-and antiinvasive agents in vitro (16,17). The data from these assays are shown in Fig.…”

Cellular processes involved in lung cancer cells exposed to direct current electric field

“…It is worth noting that different electrodes cause different chemical environments in which cells are placed. Experimental systems using platinum electrodes 72,73 and Ag-AgCl electrodes 3,4,6 can cause differences in the chemical environment in which cells are placed. Considering that the electrolysis of aqueous buffer using platinum electrodes decreases the pH at the positive electrode and decreases the pH at the negative electrode 75 .…”

“…field-induced tumor cell migration. Very recently, Ji-Yen Cheng's group conducts a study on a non-specific MMP inhibitor regulating the electrotaxis of tumor cells 6 . Three cell types are used in the study, of which human lung squamous cell carcinoma NCI-H520 cells and human large cell lung carcinoma NCI-H460 are used to represent non-small cell lung cancer (NSCLC) cells, and non-cancerous MRC-5 lung fibroblasts are considered normal cell controls.…”

“…A series of studies demonstrate that the electrotaxis of human lung adenocarcinoma CL1-5 cells with high malignancy is prominent, in contrast, the electrotaxis of human lung adenocarcinoma CL1-0 cells with low malignancy is not significant 6,10,77 . Under EF stimulation, some tumor cells undergo redirection and migration, which has potential implications for tumor metastasis 13,73,78 .…”

“…Very recently, Ji-Yen Cheng et al investigate the electrotaxis of several non-small cell lung cancers (NSCLC) strains, including human lung squamous cell carcinoma NCI-H520 cells and human large cell lung carcinoma NCI-H460. After dcEF stimulation (300-375 mV/mm, 2-6 h), lung cancer cells (NCI-H520 and NCI-H460) move towards the cathode, while non-cancerous MRC-5 lung fibroblasts migrate towards the anode 6 . Also, HE Yong et al evaluate the effects of dcEF on the migration and proliferation of lung cancer H1975 cells, and they show that the exposure of dcEF (100 mV/mm) for 1 h induces proliferation and migration of H1975 cells 12 .…”