Defense Date

2022

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

Dr. David Gewirtz

Abstract

While cancer patients often experience tumor reduction after receiving chemotherapy, tumors can eventually emerge from a state of dormancy. Cancer cells treated with the topoisomerase II poison, etoposide (ETO), enter senescence, which is a durable and prolonged cell cycle growth arrest. Different murine lung cell lines were screened for their levels of senescence induction by ETO, and those showed promising senescence induction were then treated with the senolytic, ABT263, to promote apoptosis. The hypothesis of this work was that non-small cell lung cancer cell lines will have different degrees of senescence and that the magnitude of the response to senolytics would reflect the extent of senescence induction. An additional goal of this study was to identify an appropriate mouse lung cancer line that could be used to study the interactions with the immune system. X577, E889, X381 and CMT167 cells had different degrees of senescence, and had different degrees of response to the treatment with ABT263. However, there was no clear correlation between the extent of senescence induction and the response to ABT263, and this is assumed to be due to the different genetic makeup of the cells. After analysis of the time to recovery from the treatment with ETO and ABT263, it was determined that X577 cells had the potential be investigated in vivo.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-13-2022

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