Date on Master's Thesis/Doctoral Dissertation

5-2017

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Gupta, Ramesh

Committee Co-Chair (if applicable)

Chesney, Jason

Committee Member

Chesney, Jason

Committee Member

Jun, Yan

Committee Member

Frederick Luzzio

Committee Member

Chee, Ng

Committee Member

Aqil, Farrukh

Abstract

Lung cancer is the leading cause of cancer-related deaths among both men and women in the U.S and worldwide. Today, paclitaxel (PAC) or taxol alongside platinum-based drugs is the most widely used agent as the first-line regimen for advanced NSCLC. However, due to toxicity, drug resistance, solubility and efficacy issues, efficacy has plateaued. In the present study, the potential of a novel plant-derived steroidal-lactone, withaferin A (WFA), for clinical use alongside PAC to improve efficacy against NSCLC was explored. The anticancer effects of PAC and WFA alone, and in combination against the in vitro cell proliferation, cell adhesion, migration and invasion of two human NSCLC cell lines, H1299 and A549 were determined. Our data shows that PAC and WFA, combined at 1:25 and 1:50 ratios, respectively, synergistically inhibited the proliferation of H1299 and A549 cells. Furthermore, the combination also significantly inhibited the TGFβ1-induced EMT, cell adhesion, migration, and invasion (pp

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