Radiation resistance of the lung adenocarcinoma is related to the AKT-Onzin-POU5F1 axis
| Autor: | Zhu Jin, Baoan Gao, Li Guan, Guang-Ming Xiang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Cell Biophysics Mice Nude Adenocarcinoma of Lung Adenocarcinoma Radiation Tolerance Biochemistry 03 medical and health sciences 0302 clinical medicine Cancer stem cell medicine Animals Humans Lung cancer Molecular Biology Protein kinase B Chemistry Proteins Cell Biology Transfection medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure A549 Cells 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Immunohistochemistry Ectopic expression Octamer Transcription Factor-3 Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 499:538-543 |
| ISSN: | 0006-291X |
| Popis: | Non-small cell lung carcinoma is the predominant type of lung cancer, and shows an easily developable tolerance to radiotherapy. Cancer stem cells are suggested to be involved in the resistance against therapies. Onzin might be accumulated during the process tumor overcoming the radiation stress. To address the relationship between Onzin, stemness and radiation resistance, we treated the lung cancer tumor bearing mice with radiaotherapy and observed the differences between radiation sensitive (RS) and resistant (RR) tumors. Immunohistochemistry and HE staining were used to observe Onzin and POU5F1 expression in tumor tissues. Quantitative realtime-PCR and Western blot were applied for Onzin and POU5F1 in tumors and cells. In-vitro cellular viability was assessed by CCK8 methods for tumor derived cells. The stably transfected A549 cell lines overexpressing Onzin were generated through lentivirus transfection. After radiotherapy, those RR adenocarcinoma tumors and cells derived from them showed an increased Onzin expression. Further, RR cells were found upregulated stemness, indicated by increased sphericity and proliferation, as well as POU5F1 expression. Next, we overexpressed Onzin in the A549 cells and found an elevated POU5F1 expression, increased proliferation, and enhanced sphericity. Moreover, this could be suppressed by the AKT inhibitor MK-2260. In vivo, the A549 cells overexpressing Onzin showed not only higher tumor formation capability and growth, but also a significant resistance to radiation. Taken together, RR tumors have upregulated Onzin and POU5F1 expression. Ectopic expression of Onzin promotes the POU5F1 expression as well as stemness functions, and confers adenocarcinomas the resistance to radiotherapy. |
| Databáze: | OpenAIRE |
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