Back to Search
Start Over
NFκB and TNFα as individual key molecules associated with the cisplatin-resistance and radioresistance of lung cancer
- Source :
- Experimental cell research. 374(1)
- Publication Year :
- 2018
-
Abstract
- Cisplatin-resistant (A549CisR and H292CisR) and radioresistant (A549R26 and H292R22) sub-line non-small cell lung cancer (NSCLC) cells were developed in our lab by long term treatment of parental cells with cisplatin or radiation. Our data showed no cross-resistance between these two sets of cell lines, indicating that molecular mechanisms of developing each resistance may be different. Using these sub-line cells, we sought to reveal the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, compared with parental cells. In qPCR analyses of screening DNA repair and cell survival-associated molecules, we identified NFκB and TNFα as the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, respectively, compared with parental cells. Western blot analysis of parental vs. resistant cells and the IHC staining of tumor tissues of A549P, A549CisR, and A549R26 cell-derived xenografts in mice confirmed such results. Next, studies using specific inhibitors of NFκB and TNFα and experiments using NFκB and TNFα-knocked down cells showed that inhibition or knockdown of NFκB overcame cisplatin-resistance, while inhibition or knockdown of TNFα increased radiosensitivity of radioresistant lung cancer cells. Therefore, these two molecules may be used as markers of the prognosis/diagnosis of individual resistance development during lung cancer treatment.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
DNA Repair
Cell Survival
Cell
Mice, Nude
Biology
Radiation Tolerance
03 medical and health sciences
0302 clinical medicine
Radioresistance
Cell Line, Tumor
medicine
Animals
Humans
Radiosensitivity
Lung cancer
Cisplatin
Gene knockdown
Tumor Necrosis Factor-alpha
NF-kappa B
Cell Biology
medicine.disease
Up-Regulation
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
Cell culture
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
Tumor necrosis factor alpha
Female
medicine.drug
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 374
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....9178fd0dd9eb1bc3b0bd0c5b5cc8def6