异甘草素调控LINC01503对肺鳞癌细胞的作用研究

Isoliquiritigenin Modulates the Effect of LINC01503 on Lung Squamous Carcinoma Cells

背景与目的异甘草素(isoliquiritigenin,ISL)是甘草中重要的药理成分,其具有一系列的生理和药理活性,同时具有显著的抗肿瘤活性,可以作为癌症靶向治疗的一种潜在药物。LINC01503是一种致癌基因,其与多种癌症的恶性生物学过程密切相关。本研究旨在探讨ISL通过调控LINC01503对肺鳞癌细胞增殖、凋亡、侵袭及迁移的影响。方法收集2021年1月至2022年12月于唐山市人民医院治疗的肺鳞癌患者和健康人血浆。用实时荧光定量聚合酶链式反应(real-time quantitative polymerase chain reaction,qRT-PCR)检测LINC01503在肺鳞癌血浆、组织及细胞中的表达情况。用不同浓度的ISL处理肺鳞癌细胞24 h,用qRT-PCR检测LINC01503表达情况。将细胞进行分组处理:si-NC组、si-LINC01503组、DMSO(0.1%的二甲基砜)组、ISL组、pc DNA3.1(+)-NC组、pc DNA3.1(+)-LINC01503组、ISL+pc DNA3.1(+)-NC组及ISL+pc DNA3.1(+)-LINC01503组。采用CCK-8法、克隆形成实验、流式细胞术、Transwell实验和划痕实验研究LINC01503对肺鳞癌细胞功能表型的影响。结果荧光原位杂交结果显示,肺鳞癌患者组织芯片中,肺鳞癌组织LINC01503的平均荧光强度高于癌旁组织(P<0.05)。肺鳞癌患者血浆中LINC01503的表达高于健康人血浆表达(P<0.05)。敲降LINC01503可以抑制肺鳞癌细胞的增殖、侵袭及迁移并促进调亡(P<0.05)。ISL可以抑制肺鳞癌细胞的增殖、侵袭、迁移并促进调亡(P<0.05)。过表达LINC01503后用ISL进行干预可逆转过表达LINC01503对肺鳞癌细胞的增殖、侵袭及迁移的促进作用及对调亡的抑制作用(P<0.05)。结论LINC01503在肺鳞癌中呈高表达,LINC01503可以促进肺鳞癌细胞的增殖、侵袭、迁移并抑制调亡,ISL可以通过调控LINC01503的表达抑制肺鳞癌细胞的增殖、侵袭、迁移,促进肺鳞癌细胞的凋亡。

Background and objective Isoliquiritigenin(ISL)is an important pharmacological constituent of Glycyrrhiza glabra,which possesses a range of physiological and pharmacological activities,as well as significant antitumor activity,and can be used as a potential drug for targeted cancer therapy.LINC01503 is an oncogene,which has been closely associated with the malignant biological processes of many cancers.The aim of this study was to investigate the effects of ISL on the proliferation,apoptosis,invasion and migration of lung squamous carcinoma cells by regulating LINC01503.Methods Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from January 2021 to December 2022.The expression of LINC01503 in lung squamous carcinoma plasma,tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction(qRT-PCR).Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h,and LINC01503 expression was detected by qRT-PCR.The cells were treated in groups:si-NC group,si-LINC01503 group,DMSO(0.1%dimethyl sulfone)group,ISL group,pc DNA3.1(+)-NC group,pc DNA3.1(+)-LINC01503 group,ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)-LINC01503 groups.CCK-8 assay,clone formation assay,flow cytometry,Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells.Results Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues(P<0.05).The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals(P<0.05).Knockdown of LINC01503 inhibited the proliferation,invasion and migration of lung squamous carcinoma cells and promoted apoptosis(P<0.05).ISL inhibited the proliferation,invasion,migration and promoted apoptosis of lung squamous carcinoma cells(P<0.05).Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation,invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis(P<0.05).Conclusion LINC01503 was highly expressed in lung squamous carcinoma,and LINC01503 could promote the proliferation,invasion and migration of lung squamous carcinoma cells and inhibit the apoptosis,ISL could inhibit the proliferation,invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503.