Open Access Thesis
Date of Award
Nutrition and Food Science
Dr. Smiti Gupta
Lung cancer is the leading cause of cancer death in Unites States. The main types of lung cancer are small cell lung cancer and non small cell lung cancer. NSCLC accounts for about 80% of the cases with less than 15% of patients surviving beyond 5 years. Most common causes of lung cancer are smoking, inhaling asbestos fiber, radon gas, passive smoking, air pollution, familial predisposition, prior history of lung cancer etc. Surgery, chemotherapy, targeted therapy, palliative care are commonly used treatment techniques for lung cancer. Radiation therapy is an important part of lung cancer management. The objective of this study was to investigate if δ-tocotrienol which is an isoform of essential nutrient vitamin E can be successfully used in the treatment of NSCLC. The effect of pure δ-tocotrienol was studied on NSCLC cell lines A549 and H1299. Previously it was proved that Notch-1 pathway could be a therapeutic target for NSCLC and also that pure δ-tocotrienol down regulates Notch-1 via NF -КB. This study mainly focuses on MMP-9 and uPA expression in the NSCLC cell lines via Notch-1 and HES-1. Aggregation and adhesion capability, invasive and migration ability, MMP-9 activity and molecular mechanisms like gene expression and protein expression were evaluated. Different assays like cell aggregation assay, cell adhesion assay, cell invasion assay, wound healing assay, zymogram gel assay, Real-Time PCR analysis, Western Blot analysis were performed for this purpose. A dose dependent decrease was observed in MMP-9 activity confirming its inhibition. Since there is inhibition in cell aggregation, adhesion, invasion, migration, gene and protein expressions, the study suggests that administration with pure δ-tocotrienol could be an effective approach for the treatment of NSCLC.
Pindiprolu, Rohini Sri Harshini, "Delta-Tocotrienol Downregulates Mmp-9 Expression In Nsclc Cells" (2015). Wayne State University Theses. 411.