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Nicotine induces resistance to chemotherapy in nasal epithelial cancer
- Source :
- American journal of rhinologyallergy. 24(2)
- Publication Year :
- 2010
-
Abstract
- Background Epidemiological and clinical data implicate that in patients with cancer, continued smoking causes progression of cancer growth and resistance to therapy. The carcinogens possess the ability to block apoptosis, an important mechanism in the development of tumors and resistance to chemotherapy. We previously showed that nicotine enhances growth and proliferation in lung cancer. However, the effects of nicotine, a tobacco carcinogen that inhibits apoptosis, have not been studied before in nasal epithelial carcinoma (NC). In this study, we sought to determine the effects of nicotine on chemotherapy-induced apoptosis in human NC. Methods Primary human NC cells were grown per protocol, treated with combination chemotherapy, and the apoptosis was assessed by TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) and DNA fragmentation assays. The regulation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signal transduction pathway was examined by real time quantitative polymerized chain reaction, and immunofluorescent staining assays. Results Combination chemotherapy with cisplatin (35 μM) plus etoposide (20 μM) caused a significant increase in NC apoptosis compared with single agent alone, and nicotine, in part, inhibited chemotherapy-induced apoptosis in NC. Furthermore, nicotine induced activation of AKT and MAPK pathways, while inhibition of MAPK using U0126 and AKT by phosphatidylinositol 3-kinase inhibitor, LY294002, in part, blocked the antiapoptotic effects of nicotine against cisplatin and etoposide-induced apoptosis in NC. Conclusion Nicotine inhibits chemotherapy-induced apoptosis in NC via the AKT and MAPK-mediated signaling pathways. We speculate that nicotine may play a role in oncogenesis and resistance to cancer therapy in NC.
- Subjects :
- Nicotine
Morpholines
Nose Neoplasms
Apoptosis
Cell Line, Tumor
Nitriles
medicine
Butadienes
Immunology and Allergy
Humans
Protein kinase B
Etoposide
Cisplatin
TUNEL assay
business.industry
Smoking
Cancer
Combination chemotherapy
General Medicine
medicine.disease
Oncogene Protein v-akt
Otorhinolaryngology
Chromones
Drug Resistance, Neoplasm
Cancer research
Carcinogens
Carcinoma, Squamous Cell
Disease Progression
Signal transduction
Mitogen-Activated Protein Kinases
business
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 19458932
- Volume :
- 24
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of rhinologyallergy
- Accession number :
- edsair.doi.dedup.....c1063087849c464b1a189cc3362ce87d