| | Category | BI | L06 | Investigating Drug Resistance in MCF7 WT and MCF60 Breast |
| | Cancer Cell Lines |
| | Abstract | Breast cancer is the second most common cause of death for women |
| | worldwide. Every year in the United States, 200,000 women and men are |
| | diagnosed with breast cancer. Arsenic trioxide (As2O3) is currently used |
| | to treat many types of cancer such as acute promyelocytic leukemia, and |
| | the probable curative application of As2O3 to breast cancer is being |
| | researched. Currently, cancer cells’ drug resistance to arsenic poses as a |
| | major obstacle in the treatment of cancer. |
| | The purpose of my project was to identify the arsenic transport systems |
| | present in both wild type and arsenic resistant breast cancer cell lines |
| | (MCF7 and MCF60 cell lines respectively). This project also investigated |
| | the biochemical properties of the MCF60 arsenic resistant cell line in |
| | comparison to the wildtype MCF7 line and determined the rate of uptake |
| | and efflux of arsenic in both cell lines. MTT assays, transport experiments, |
| | RNA isolation, and RT-PCR were all methods that were used to investigate |
| | drug resistance and uptake. MTT assays were conducted to determine |
| | cell counts after other cancer treating drugs such as doxorubicin and |
| | etoposide were added to the cells for several days. EC50 values were |
| | used as a comparison between the two cell lines and greater viable cell |
| | counts were found from the MCF60 resistant cell line in comparison to the |
| | MCF7 wild type cell line when treated with arsenic, antimony, and |
| | pretreated with a BSO inhibitor. Transport experiments on the MCF7 cell |
| | line were conducted to determine the cell’s rate of uptake at certain time |
| | intervals. RNA was also isolated and reverse transcribed into cDNA, so |
| | that the genes and proteins involved in arsenic resistance/efflux and |
| | uptake were determined. The aquaporin protein AQP9 was found to |
| | possibly play a role in arsenic uptake and efflux. |
| | Overall, the results of this study suggest that the presence of AQP9 |
| | plays a role in the cell’s resistance to arsenic, as well as other drugs such |
| | as antimony. It also concludes that the protein MRP is not involved in the |
| | extrusion system of the MCF60 cell. This knowledge can help to solve the |
| | problem of drug resistance and help continue the treatment of breast |
| | cancer cells using heavy metals such as AsIII. |
| | Bibliography | Arsenic Trioxide in the mechanism of drug resistance reversal in MCF- |
| | 7/ADM cell line of human breast cancer. Wang X, Kong L, Zhao J, Yang P. |
| | PubMed: 152836393.Differential effects of quercetin and silymarin on |
| | arsenite-induced cytotoxicity in two human breast cancer cell lines. Soria |
| | EA, Eynard AR, Quiroga PL, Bongiovanni GA. PMID: 17931660 |