[Fatty acids regulate macrophage polarization to inhibit the growth and metastasis of lung cancer cells induced by intermittent hypoxia].

Objective: To investigate the effects of lipid metabolism on the polarization of macrophages and proliferation and migration of lung cancer cells under intermittent hypoxia. Methods: THP-1 cells were treated with 100 ng/mL phorbol ester (PMA) for 48 h to induce differentiation into M0 macrophages, and 20 ng/mL interleukin (IL)-4 for 24 h to induce polarization of macrophages under room air (RA) or chronic intermittent hypoxia (CIH) environment. The mRNA levels of CD86, tumor necrosis factor α (TNF-α), CD206 and IL-10 in macrophages were detected by real-time quantitative polymerase chain reaction (qRT-PCR) after the intervention of palmitic acid (PA) and arachidonic acid (AA). A549 cells were co-cultured with supernatant and divided into six groups: RA control, RA-PA, RA-AA, CIH control, CIH-PA and CIH-AA. The proliferation rate of A549 cells was detected by CCK-8 method. Cell migration ability was detected by scratch test and Transwell. The protein expression of MMP2 and MMP9 was detected by western blot. The expression levels of PA, AA, TNF-α and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Results: After treating A549 cells with supernatants from macrophages under RA and CIH conditions, the results showed that compared with the RA control group [(0.59±0.02)%], the cell proliferation activity in the CIH control group [(0.85±0.01)%, P＜0.001] increased. Compared with the RA control group, the CIH control group exhibited enhanced cell migration and invasion abilities [RA control group: migration rate (48.55±0.19)%, number of invasive cells (47.33±1.53); CIH control group: (61.94±0.39)%, (77.33±2.08); P＜0.001]. Additionally, the protein levels of MMP2, MMP9 and IL-10 increased (all P＜0.05), while the contents of PA, AA, and TNF-α decreased (all P＜0.05). Compared with the CIH control group [(0.85±0.01)%], the CIH-PA group [(0.70±0.01)%] and the CIH-AA group [(0.66±0.01)%] showed reduced cell proliferation ability (P＜0.001). Their migration and invasion abilities also decreased [CIH control group: migration rate (61.94±0.39)%, number of invasive cells (77.33±2.08); CIH-PA group: (55.11±0.10)%, (57.00±1.00); CIH-AA group: (55.95±0.17)%, (55.67±1.53), P＜0.001]. Furthermore, the levels of MMP2, MMP9 proteins, and IL-10 decreased (all P＜0.05), while the contents of PA, AA, and TNF-α increased (all P＜0.05). Conclusion: PA and AA reduce the proliferation, metastasis and invasion of lung cancer cells induced by CIH by inhibiting the M2-type polarization of macrophages.