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极光激酶 A/NF-κB 信号与人类肺腺癌的放射抵抗有关。

Aurora-A/NF-ĸB Signaling Is Associated With Radio-resistance in Human Lung Adenocarcinoma.

机构信息

Traditional Chinese Medicine Department, People's Hospital of Henan Province, People's Hospital of Zhengzhou University, Zhengzhou, P.R. China.

Department of General Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, P.R. China.

出版信息

Anticancer Res. 2019 Nov;39(11):5991-5998. doi: 10.21873/anticanres.13804.

DOI:10.21873/anticanres.13804
PMID:31704824
Abstract

BACKGROUND/AIM: This study aimed to discuss the effect and possible molecular mechanisms of Aurora-A/NF-ĸB signaling on the radiotherapy resistance of human docetaxel-resistant lung adenocarcinoma cells.

MATERIALS AND METHODS

The human lung adenocarcinoma SPC-A1 and SPC-A1/DTX cell lines were utilized in the present study. The MTT assay measured the sensitivity of cells to radiotherapy. The tumor-initiating ability of the cells was detected in vitro by cloning assays. Apoptosis was quantified by flow cytometry. Real-time quantitative PCR and western blotting were used to detect the mRNA and protein expression of the Aurora-A/NF-ĸB, respectively. Tumors transplanted subcutaneously into nude mice were used to test the effect of Aurora-A on the in vivo sensitivity of the tumors to radiotherapy.

RESULTS

The SPC-A1/DTX docetaxel-resistant lung adenocarcinoma cells were radio-resistant compared with the parental SPC-A1 cells. Up-regulated aurora-A was responsible for the in vitro radio-resistance of docetaxel-resistant SPC-A1/DTX cells. Nuclear transcription factor NF-ĸB was identified as a downstream target gene of Aurora-A in SPC-A1/DTX cells, and NF-ĸB also participated in the radio-resistance of SPC-A1/DTX cells regulated by Aurora-A.

CONCLUSION

The Aurora-A/NF-ĸB pathway is association with radio-resistance of human lung adenocarcinoma docetaxel-resistant cells.

摘要

背景/目的:本研究旨在探讨 Aurora-A/NF-κB 信号对人 docetaxel 耐药肺腺癌细胞放射抵抗的作用及可能的分子机制。

材料与方法

本研究采用人肺腺癌细胞系 SPC-A1 和 SPC-A1/DTX。MTT 法检测细胞对放射治疗的敏感性。克隆实验检测细胞的体外成瘤能力。流式细胞术检测细胞凋亡。实时定量 PCR 和 Western blot 分别检测 Aurora-A/NF-κB 的 mRNA 和蛋白表达。皮下移植裸鼠肿瘤检测 Aurora-A 对肿瘤体内放射敏感性的影响。

结果

与亲本 SPC-A1 细胞相比,SPC-A1/DTX 多西紫杉醇耐药肺腺癌细胞具有放射抵抗性。上调的 Aurora-A 是多西紫杉醇耐药 SPC-A1/DTX 细胞体外放射抵抗的原因。核转录因子 NF-κB 被鉴定为 SPC-A1/DTX 细胞中 Aurora-A 的下游靶基因,NF-κB 也参与了 Aurora-A 调节的 SPC-A1/DTX 细胞的放射抵抗。

结论

Aurora-A/NF-κB 通路与人类肺腺癌细胞多西紫杉醇耐药细胞的放射抵抗有关。

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