Lung cancer is a significant cause of mortality in the U.S., the leading among cancer deaths, and more research is needed to improve the clinical picture for patients. Drug resistance remains a barrier to successful treatment of cancer even with the ongoing development of new molecularly targeted therapies. In the diagnosis of cancer, the treatment is determined based on the parameters of the tumor. Non-invasive cancers are often cured by surgery alone, while cancers that have progressed past the lymph node stage are commonly treated with chemotherapy. Chemotherapy drugs are administered systemically and used to kill cancer cells and prevent cancerous cells from producing. There is not a definitive way to distinguish between a chemotherapy resistant or sensitive cancer tumor at the time of diagnosis which is wasting precious time for the patient if the treatment does not work. The main goal of the Skildum lab is to identify biomarkers specific for drug resistant cancer that will allow for earlier and more effective treatment decisions.
We have established a model of cancer resistance, using MCF-7 (sensitive to chemotherapy) and LCC9 (less sensitive to chemotherapy treatment) breast cancer cells. We have shown that LCC9 cells have increased mitochondrial capacity and increased expression of the Tfam gene in comparison to the MCF-7 counterpart. Tfam is a major regulator of mitochondrial DNA replication and transcription. From here curiosity struck to discover if other forms of cancer have increased expression of the Tfam gene in the resistant form of cancer. If we are able to discover a gene that is uniquely expressed in a number of cancers, we may be able to target that gene as a biomarker in the diagnosis of cancer patients.
The goal of the current work was to test whether mitochondrial capacity was elevated in a model of doxorubicin resistant human lung cancer. The techniques used were cell culture, sulforhodamine B assay and hemocytometer to verify doxorubicin treatment in the cells, DNA isolation for mtDNA expression and RNA isolation to express Tfam through qPCR. Preliminary results show that chemotherapy resistant lung cancer cells have increased mitochondrial DNA and Tfam expression in comparison with their sensitive lung cancer counterpart.
This research was supported by the Undergraduate Research Opportunities Program (UROP).
Mitochondrial capacity of chemotherapy resistant and sensitive lung cancer cells.
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