放疗通过上调lincRNA-p21改变肿瘤相关巨噬细胞的极化,抑制肺癌进展

Wanru Geng, Yu Sun, Yan Jiang, K. Sun
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引用次数: 2

摘要

目的:有报道称肿瘤中肿瘤相关巨噬细胞(tumor associated macrophages, tam)数量高与肿瘤对辐照的不良反应相关。然而,很少有研究试图证明tam在放疗中抑制肺癌进展的作用。方法:从接种Lewis肺癌细胞并接受放射治疗的C57BL/6小鼠中分离tam,采用qPCR方法分析极化巨噬细胞maker基因和lincRNA-p21的表达。分别用CKK-8法和细胞侵袭法检测TAMs培养的Lewis细胞辐照后的细胞活力和侵袭性。我们使用Ad-LincRNA-p21和Ad-Si-LincRNA-p21来检测lincRNA-p21对tam的影响。结果:放疗能有效抑制Lewis肺癌细胞移植后C57BL/6小鼠的肿瘤生长。放疗促进tem向M1巨噬细胞极化,上调tem中lincRNA-p21水平。此外,转染Ad-LincRNA-p21的tem具有抗肿瘤作用,Ad-Si-LincRNA-p21可能逆转放疗对肿瘤生长的影响。结论:我们的研究结果提示放疗促进tem向M1巨噬细胞极化,抑制肺癌进展,lincRNA-p21在肺癌放疗治疗中发挥重要作用。关键词:放射治疗;极化;肿瘤相关巨噬细胞;肺癌;lincRNA-p21
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Radiotherapy alters the polarization of tumor-associated macrophage to suppress lung cancer progression via up-regulation of lincRNA-p21
Objective : It has been reported that high tumor-associated macrophages (TAMs) numbers in tumors were correlated with poor tumor responses to irradiation. However, few studies have attempted to demonstrate the roles of TAMs in radiotherapy for suppressing the progression of lung cancer. Methods : TAMs were separated from C57BL/6 mice which were inoculated Lewis lung cancer cells and exposed to radiation therapy, then the expression of maker genes of polarized macrophages and lincRNA-p21 were analyzed using qPCR. Cell viability and invasion of Lewis cells cultured with TAMs exposed to radiation therapy were detected with CKK-8 assay and cell invasion assay, respectively. Ad-LincRNA-p21 and Ad-Si-LincRNA-p21 were used to examine the effect of lincRNA-p21 on TAMs. Results : Radiotherapy effectively suppressed the tumor growth in C57BL/6 mice transplanted with Lewis lung cancer cell. Radiotherapy promoted the polarized of TEMs into M1 macrophage and up-regulated the level of lincRNA-p21 in TEMs. Moreover, TEMs transfected with Ad-LincRNA-p21 presented anti-tumor effect and Ad-Si-LincRNA-p21 might reverse the effect of radiotherapy on tumor growth. Conclusion : Our results suggest that radiotherapy promotes the polarization of TEMs into M1 macrophage to suppress lung cancer progression and lincRNA-p21 plays an important role in the radiotherapy treatment for lung cancer. Keywords:  radiotherapy; polarization; tumor-associated macrophage; lung cancer; lincRNA-p21
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