靶向SECTM1抑制低浓度帕博西尼诱导的肺腺癌细胞恶性表型

Targeting SECTM1 to inhibit the malignant phenotype induced by low-concentration of Palbociclib in lung adenocarcinoma cells

目的:探讨敲低分泌及跨膜蛋白1(secreted and transmembrane 1,SECTM1)对低浓度细胞周期选择性抑制剂帕博西尼(Palbociclib,Pb)诱导的肺腺癌细胞恶性表型的逆转作用。方法:CCK8法检测不同浓度Pb对肺腺癌细胞系H1650的杀伤作用;Transwell小室实验检测2μmol/L Pb处理H1650细胞后侵袭、迁移能力的变化;生物信息学分析2μmol/L Pb处理H1650细胞后转录组表达变化并筛选差异基因;验证Pb对H1650细胞SECTM1表达量的影响,检测敲降SECTM1对低浓度Pb诱导的恶性表型及上皮间质转化标志物的逆转作用。结果:Pb可抑制H1650细胞生长,但2μmol/L Pb处理显著促进其侵袭能力、迁移能力;测序结果显示,2μmol/L Pb处理后抑制H1650细胞细胞周期相关信号通路,但促进了细胞因子-细胞因子受体相关通路的激活;敲降SECTM1显著逆转了低浓度Pb诱导的细胞侵袭、迁移能力及上皮间质转化标志物的增加。结论:低浓度Pb可能诱导肺腺癌细胞侵袭、迁移能力增加,靶向敲低SECTM1可抑制其副作用。

Objective:To investigate the reversal effect of knockdown of secreted and transmembrane 1(SECTM1) on the malignant phenotype of lung adenocarcinoma cells induced by low-concentration of Palbociclib(Pb),a cell cycle selective inhibitor.Methods:The killing effect of different concentrations of Pb on lung adenocarcinoma cell line H1650 was detected using CCK8.Transwell chamber experiment was used to detect the invasion and migration ability of H1650 cells after 2 μmol/L Pb treatment.Bioinformatics analysis was used to analyze transcriptome expression changes and screen for differentially expressed genes after 2 μmol/L Pb treatment to H1650 cells.The effect of Pb on the expression level of SECTM1 in H1650 cells was verified.The effect of SECTM1 knockdown on the malignant phenotype and epithelial-mesenchymal transition(EMT) markers induced by low-concentration of Pb was further detected.Results:Pb inhibited the growth of H1650 cells but 2 μmol/L Pb promoted their invasion and migration abilities.The sequencing results showed that 2 μmol/L Pb inhibited the cell cycle related signaling pathways in lung adenocarcinoma cells,but activated the cytokine-cytokine receptor interaction pathway.Knockdown of SECTM1 significantly reversed the increase in low-concentration of Pb-induced invasion and migration abilities and decreased the expression of EMT markers.Conclusion:Low-concentration of Pb may induce increased invasion and migration ability of LUAD cells,and targeting SECTM1 might inhibit its side effects.