RESUMO
Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Senescência Celular , Neoplasias Pulmonares , Tolerância a Radiação , Receptores Imunológicos , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Senescência Celular/efeitos da radiação , Tolerância a Radiação/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Animais , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Camundongos , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Fenótipo Secretor Associado à Senescência/genética , Células A549 , FemininoRESUMO
Non-antibiotic substances have been found to contribute to the spread of antibiotic resistance. Bromophenols (BPs) are special anti-bacterial substances obtained from seaweed. This study explored the modulatory effect of trace BPs from a live seaweed on the antibiotic resistance of pathogenic Vibrio (V.) strains. A hydroponic solution of Ulva fasciata was found to contain trace levels (9-333 µg L-1) of 2,4,6-tribromophenol (TBP), a typical BP. TBP at a concentration of 165 µg L-1 significantly increased the inhibition zone diameter of widely used ß-lactam antibiotics (amoxicillin and ampicillin) against V. alginolyticus M7 (Va. M7) and V. parahaemolyticus M3 (Vp. M3) as well as reduced the minimum inhibitory concentration by 2-4 fold against Va. M7. Whole genome re-sequencing analysis demonstrated that Va. M3 (53-60) had more mutant genes than Vp. M7 (44) in ß-lactam resistance pathway. Transcriptome sequencing analysis, along with verification through RT-qPCR, further showed that oligopeptide permease (opp) was the only differentially expressed gene (DEG) among the mutated genes in the ß-lactam resistance pathway. The opp transport activity and membrane permeability of Vibrio were both enhanced at 165 µg L-1 of TBP, and the ability of biofilm formation was also decreased. Thus, antibiotics resistance improvement of Vibrio by TBP was potentially related with the promoted opp transport activity, membrane permeability and inhibited biofilm formation.