1. The Role of Survivin in Nicotine-Related, Drug-Resistant Lung Cancer
Jenny Mu
Bergen County Academies
Abstract
Nicotine has been shown to confer resistance to anti-cancer drugs, making
nicotine related lung cancer cases difficult to address. Survivin is an anti-apoptosis
protein that has been shown to be an ideal target for cancer gene therapy, and aberrant
behavior of the protein is associated with a drug-resistant phenotype in cancer cells.
In this study, the role of survivin in nicotine-related, drug-resistant lung cancer was
investigated. Survivin mRNA expression was silenced in nicotine-treated A549 cells, and
doxorubicin resistance was measured. Additionally, a possible mechanism of nicotine-
mediated doxorubicin-resistance was elucidated. The effect of survivin knockdown on
EGFR-phosphorylation and chemotactic response to epidermal growth factor was
examined as a potential mechanism of doxorubicin resistance. From the results of this
study, it was shown that survivin is a method through which nicotine confers doxorubicin
resistance to cancerous cells. It was also concluded for the first time that silencing of
survivin mRNA expression inhibits activation of EGFR in lung cancer cells independent
of EGF ligand binding. The results of this experiment show that silencing of survivin
mRNA expression diminishes nicotine-related doxorubicin resistance, suggesting both a
potential treatment for drug-resistant lung cancers, and a novel explanation for
mechanisms of action.