IL-33在肺腺癌组织中表达变化及其对肺腺癌PC-9细胞增殖能力的影响OACSTPCD

Objective To observe the expression changes of interleukin-33(IL-33)in the lung adenocarcinoma tis-sues and its effect on the proliferation of lung adenocarcinoma PC-9 cells,and to explore whether its mechanism is related to affecting the polarization of tumor-associated macrophages(TAM)and the cytotoxic effect of CD8+T lymphocytes.Methods Ninety-one patients with lung adenocarcinoma who underwent radical resection of lung cancer and were patho-logically diagnosed were selected.During the operation,their lung adenocarcinoma and adjacent tissues were collected.Immunohistochemistry and Western blotting were used to detect the expression levels of IL-33 and CD206.The positive ex-pression rates of IL-33 and CD206 in patients with different clinical characteristics were compared,and the correlation be-tween the two was analyzed.The infiltration of CD206+TAM in IL-33-positive and-negative lung adenocarcinoma tissues was compared(expressed by the specific fluorescence intensity of CD206).The human monocytic leukemia cell line(THP-1)in the logarithmic growth phase were selected and were induced to M0 TAM by adding phorbol ester;after that,they were divided into the groups A,B,C,and D,respectively,and were cultured with 0,5,10,15 ng/mL IL-33 for 2 days.The expression rates of CD206,CD163,CD80 and CD86 were detected by flow cytometry.We co-cultured the lung adenocarcinoma PC-9 cells with the supernatant of TAM in each group for 2 days,and then detected the expression of Ki67 in lung adenocarcinoma PC-9 cells by flow cytometry.CD8+T lymphocytes were isolated and co-cultured with the superna-tant of TAM in each group for 2 days.The positive rates of IFN-γ,Perforin and Gzmb in CD8+T lymphocytes were detect-ed by flow cytometry.Results The positive expression rates and relative protein expression levels of IL-33 and CD206 in the lung adenocarcinoma tissues were higher than those of the adjacent tissues,and the relative protein expression levels of IL-33 and CD206 in lung adenocarcinoma tissues were positively correlated(r=0.617,all P<0.05).The positive expres-sion rates of IL-33 and CD206 in lung adenocarcinoma tissues of patients with poor differentiation,lymph node metastasis N1-3 stage and clinical stage Ⅲ were higher than those of patients with moderate/well differentiation,lymph node metasta-sis N0 stage and clinical stage Ⅰ/Ⅱ(all P<0.05).The specific fluorescence intensity of CD206 in IL-33 positive and nega-tive lung adenocarcinoma tissues was 12.42±1.46 and 4.23±1.01,respectively,with statistically significant difference(P<0.05).The expression rates of CD206 and CD163 in the TAM of groups A,B,C,and D increased successively,while the expression rates of CD80 and CD86 decreased successively(all P<0.05).The expression rates of Ki67 in PC-9 cells co-cultured with the supernatant of TAM of groups A,B,C,and D increased in turn,while the positive rates of IFN-γ,Perforin,and Gzmb in CD8+T lymphocytes decreased successively(all P<0.05).Conclusions The expression of IL-33 increases in the lung adenocarcinoma tissues and is related to disease progression.IL-33 can promote the proliferation of lung adenocarcinoma cells.The mechanism may be related to inducing M0-type macrophages to polarize into M2-type TAM and inhibiting the cytotoxicity of CD8+T lymphocytes.