Studies of a novel drug designed to prevent tumor invasion and metastasis
Slutsky, Audrey Louise
MetadataShow full item record
Anti-invasive therapeutics provide a means to improve the prognosis of invasive cancer patients. Recently, one such compound have been identified for its ability to halt the invasion of glioblastoma. This compound, known as Imipramine Blue (IB), successfully reduced cancer cell invasion in vitro and in vivo, and displayed the potential to reduce invasion in other invasive cancer models as well.1 Therefore, it was determined that the effects of IB should be studied in depth on other invasive cancer models, and a metastatic prostate cancer cell line, MatLyLu, was chosen for the study. Prostate cancer, like glioblastoma, has a poor prognosis due to its extremely invasive nature. The primary goal of this project was to determine the ability of IB to halt invasion of the MatLyLu cell line at non-cytotoxic levels. To do this, an in vitro invasion assay was performed on MatLyLu. Preliminary results showed that MatLyLu experiences a dose dependent decrease in invasion, but for this experiment, IB was determined to be cytotoxic. Thus, the invasion assay procedure was then optimized to eliminate cytotoxicity, and any possible human error. The invasive glioblastoma cell line, which has been shown to respond to IB treatment, was also incorporated as a positive control. Another test was performed, and results showed that IB was no longer cytotoxic. However, a dose dependent decrease in invasion was no longer seen for either cell line. The invasion assay procedure was optimized further, and the experiments were performed again. Results from these experiments showed that the RT2 cells do experience a dose dependent decrease in invasion at non-cytotoxic levels. However, the MatLyLu cell line still did not show a dose dependent decrease in invasion. The secondary goal of this project was to develop an in vivo tumor model for MatLyLu. A metastatic model was developed in Copenhagen rats, and the model develops metastases in the lungs 18 days after tumor cell implantation. This model must be tested with Luciferase expressing MatLyLu cells in order to evaluate metastasis non-invasively.