Pancreatic cancer remains a disease with an incredibly high mortality rate since it is virtually undetectable in its early stages and is difficult to treat with current therapies in later stages. The gene high mobility group AT-hook 1 (HMGA1) is upregulated in this type of cancer, which increases the resistance to chemotherapy and increases tumor growth. By engineering a viral vector that is specific to pancreatic cancer and is able to decrease HMGA1 levels within the cell, cancer cell viability is reduced drastically. However, it is important to ensure that this viral vector only targets pancreatic cancer cells, rather than other tissues in the body or healthy pancreatic cells. To test whether the current engineered oncolytic viral vector is specific to only cancerous cells, two viral vectors each were tested among three different cell lines: the MIA PaCa-2 and AsPC-1 pancreatic cancer cell lines and the breast cancer cell line MCF-7. One viral vector was engineered with a CMV promoter and the other utilized a Ptf1a promoter within the plasmid. These promoters were used in conjunction with a gene for green fluorescent protein, in order to determine whether the virus is able to decrease cell viability in pancreatic cancer cells and if it is specific only to pancreatic cancer cells. Although data was not able to be collected due to the current situation, the expected results from fluorescence spectroscopy would hopefully indicate that fluorescence is observed within MIA PaCa-2 and AsPC-1, but not in MCF-7 with the Ptf1a promoter. Furthermore, decreased levels of HMGA-1 are desired within the pancreatic cancer cell lines after inoculation with the virus, indicating reduced cell viability, as shown by Western Blotting. This is a novel approach to attacking and reducing the mortality rate of pancreatic cancer, without harming healthy tissue in the process.
Author: Alexa VanderHoff
Faculty Advisor: Dr. Michael Kennedy, Department of Chemistry and Biochemistry
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