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RETRACTED: FASN-TGF-β1-PD-L1 axis contributes to the development of resistance to NK cell cytotoxicity of cisplatin-resistant lung cancer cells
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1863:313-322
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Cisplatin remains the most effective therapy for non-small cell lung cancer (NSCLC). We previously have found cisplatin-resistant lung cancer cells (A549CisR and H157CisR) were more resistant to natural killer (NK) cell-mediated cytotoxicity than parental cells. We also discovered that fatty acid synthase (FASN) levels in cisplatin-resistant cells were significantly higher than in parental cells. To reveal whether a link exists between the up-regulated FASN levels and higher resistance to NK cell cytotoxicity, we performed inhibition studies using a FASN inhibitor and applied the FASN knockdown approach. In both approaches, we found that the FASN inhibition/knockdown significantly increased the susceptibility of cisplatin-resistant cells to NK cell cytotoxicity. We further found such decreased susceptibility was associated with an increased programmed death receptor ligand (PD-L1) level in cisplatin-resistant cells. In mechanisms studies, TGF-β1 was found to be the FASN downstream signaling molecule that was responsible for modulating the PD-L1 levels in cisplatin-resistant cells. Accordingly, TGF-β1 inhibition resulted in significantly increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity. We suggest that the inhibition of FASN-TGFβ1-PD-L1 axis may improve the efficacy of immunotherapy in treating cisplatin-resistant lung cancer.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
medicine.medical_treatment
B7-H1 Antigen
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
PD-L1
medicine
Humans
Lung cancer
Receptor
Cytotoxicity
Molecular Biology
Cisplatin
Immunity, Cellular
Gene knockdown
biology
Chemistry
Cell Biology
Immunotherapy
medicine.disease
Neoplasm Proteins
Fatty Acid Synthase, Type I
Killer Cells, Natural
Fatty acid synthase
030104 developmental biology
A549 Cells
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
biology.protein
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 13881981
- Volume :
- 1863
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Accession number :
- edsair.doi.dedup.....ee7958e8555da71950b7951bef8550a9