The influence of brown adipose tissue on the proliferation and chemosensitivity in non-small cell lung cancer cells

Abstract

Introduction: Lung cancer patients often experience cancer cachexia (CC) in the course of their progressive disease. The presence of CC is associated with both reduced tolerance to anticancer therapy and shorter patient survival. Brown adipose tissue (BAT) and its derived adipokines may play a crucial role in the development of CC and resistance of chemotherapy in lung cancer patients. Objectives: We aimed to find out whether BAT derived medium affect proliferation and cisplatin-induced apoptosis in non-small cell lung cancer (NSCLC) cells. Methods: Six NSCLC cell lines (H1299, A549, H322, PC-9, H1650, H460) were subjected to BAT culture medium after 24 hours of standard medium culture. Additionally, NSCLC cells were treated with cisplatin for 72 hours. For each NSCLC cell line, short-term effects of BAT medium and cisplatin treatment on proliferation via MTT assay and apoptosis via annexin V5 assay by flow cytometry. Starvation was simulated by reduced medium serum concentration (0.2%). Results: PC-9 and H1299 cells showed significantly increased cell counts after 72h of incubation in BAT medium compared with control medium independent of starvation condition. Cisplatin-induced reduction of proliferation in H1299 cells was partially abolished by BAT medium. The cell death rate in all NSCLC cells decreased when cisplatin treated cells were cultured in BAT medium in contrast to control medium. Conclusions: BAT medium increases cell proliferation and reduces chemosensitivity in NSCLC cells. BAT might induce tumour progression potentially via specific adipokine signalling. BAT-derived adipokines, therefore, might mediate not only CC, but also tumour growth in NSCLC.