Effectiveness of Metformin in Cancer Chemotherapy in Drosophila Melanogaster
Link to poster: Project Presentation Poster
During the summer of 2019, I completed a research internship with Professor Michele Markstein at her lab at the University of Massachusetts, Amherst. I learned how tumor growth and treatment are investigated and performed wet-lab experiments to study cancer in the fruit fly (Drosophila Melanogaster). The fruit fly genome is 60% homologous to that of humans. Also, about 75% of genes that cause human diseases have homologs in flies. In addition, the fly’s short reproduction cycle helps us study the complex pathways in tumor growth and the response to drugs in a short time. Prof. Markstein and her research staff taught me how to use the Gal4-UAS system to direct gene expression in specific cells, determine MRP expression through the Green Fluorescent Protein (GFP), set up genetic crosses to determine the survival of mutant flies without MRP, induce cancer in flies, and dissect fly intestines to view cancerous tissues.
After this initial training, I completed an extensive literature review on the effectiveness and toxicity of different chemotherapeutic drugs. I discovered that an inexpensive diabetes drug, Metformin, had been found to improve the effectiveness of chemotherapeutic drugs. I also learned that a very effective chemotherapeutic drug, Vincristine, is very toxic, and another moderately effective drug, Rapamycin, is non-toxic. So, I decided to investigate if Metformin can help retain the effectiveness of Vincristine while lowering its toxicity, and if it can increase the effectiveness of Rapamycin while retaining the non-toxicity. I also decided to investigate this effect on both wild and mutant fruit flies. I set up a detailed set of experiments. With the help of the research staff, I executed these experiments by feeding drugs at scheduled times, performing dissections to extract the cancerous intestines, and observing them under a confocal microscope. I analyzed the microscopy images from each experiment and estimated the effectiveness of the drug combinations on cancer growth. Results indicate that the tumor cells were not affected by the presence or absence of MRP and that Metformin improved the effectiveness of Rapamycin while lowering the toxicity of Vincristine.