Degree Type
Honors Capstone Project
Date of Submission
Spring 5-1-2012
Capstone Advisor
Sandra G. Hudson
Honors Reader
Thomas P Fondy
Capstone Major
Biology
Capstone College
Arts and Science
Audio/Visual Component
no
Capstone Prize Winner
no
Won Capstone Funding
yes
Honors Categories
Sciences and Engineering
Subject Categories
Biology | Cancer Biology | Cell Biology
Abstract
Cancer is a group of diseases characterized by abnormal control of cell growth and cell survival. Current treatment for cancer employs a combination of modalities including surgery, radiation, chemotherapeutic drugs, and immunotherapy. Our lab focuses on personalized medicine and treatments that can specifically target molecular features of a tumor as presented by the particular patient being treated. Cancers often exhibit an over-expression or under-expression of certain proteins that play a large role in regulating the process of apoptosis, which is programmed cell death. This study focuses on proposing drug treatment for cancer that is personalized in that it targets a protein family that is often over-expressed. This study was conducted on four human breast cancer lines: MDA-468, MDA-231, BT-20 and T47D. The protein family studied was the BCL-2 family member proteins which are divided in pro- and anti- apoptotic proteins. Two of the four cell lines were characterized by an over-expression of anti-apoptotic proteins which offers an option for specific targeted treatment by invoking inhibition of the over-expressed proteins. A small molecule BCL-2 inhibitor, Obatoclax (GX15-070) was used in this study in combination with radiation therapy to observe the effects on growth of these cancerous cells and to determine whether apoptosis was induced. This study shows that Obatoclax and radiation in combination is more effective inducing apoptosis in neoplastic cells lines that over-express anti-apoptotic BCL-2 family members. This finding is significant because it demonstrates the potential value of personalized, specific targeted treatment. Not all tumors have an over-expression of anti-apoptotic BCL-2 family members, therefore Obatoclax would not be an effective treatment for such cancers. Since this drug would be most effective in treating tumors with an over-expression of anti-apoptotic BCL-2 family members, this study proposes a method to discover which tumors may over-express anti-apoptotic BCL-2 family members and allows for quantification. This allows for the specific personalized treatment of certain cancers and may be a more effective approach to treatment than just the standard treatment options.
Recommended Citation
Howard, Amari Sasha, "Effect of Combining Bcl-2 Inhibition and Radiation on Apoptotic Cell Death in Human Breast Cancer Cell Lines as Determined by Clonogenic Assay and Western Blots" (2012). Renée Crown University Honors Thesis Projects - All. 141.
https://surface.syr.edu/honors_capstone/141
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