09 Jul How might nicotine inhibit apoptosis in the presence of chemotherapeutic drugs?
Cigarette smoking is a major risk factor in the development of non-small cell lung cancers (NSCLC), which account for 80% of lung cancers. This cancer has a poor prognosis and is resistant to chemotherapy. To understand if nicotine affects this resistance, lung cancer cell lines were treated with the three different chemotherapeutic drugs (gemcitabine, cisplatin, and taxol) in the presence and absence of nicotine. Data is shown below in the left-most graph. Three different NSCLC cell lines were used: A549 (white), NCI-H23 (dark grey or blue), and H1299 (light grey). After being exposed to the treatments indicated below a TUNEL assay was performed. TUNEL assays are used to detect cells that are undergoing apoptosis (programmed cell death). If a cell is “TUNEL Positive” it is apoptotic.
a. Why are these chemotherapeutic drugs potentially useful for the treatment of lung cancer (remember the EXPERIMENT WAS PERFORMED ON lung cancer cell lines!)? Rubric (0.5): Explain the result when each chemotherapeutic drug alone (0.25 pts) was applied to the cells and explain why these drugs might be useful given the result (0.25pts)
b. How does nicotine affect the usefulness of the cancer fighting drugs? Rubric (0.5): Explain the result when the therapeutic drugs were given in the presence of nicotine (0.5pts).
c. Survivin and XIAP are proteins that inhibit apoptosis in the cell. Researchers systematically depleted survivin or XIAP protein in cells using siRNA. This is a common technique used in cell biology that results in a loss of function (no or low levels of a specific protein) phenotype in the cells. The graph below (right) depicts the result of A549 cells were either untreated (None) or transfected with a control siRNA (should have no effect), XIAP-siRNA, Survivin-siRNA, or a combination of XIAP and survivin siRNA. Next the cells were cultured in the presence of nicotine, Gemcitabine, or gemcitabine and nicotine. The control cells experienced normal cell culture conditions but were untreated. What does this study suggest about the mechanism of nicotine action? Rubric (0.5): How might nicotine inhibit apoptosis in the presence of chemotherapeutic drugs?
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