NIH Research Festival
Cisplatin, carboplatin, and oxaliplatin are the most widely used class of cancer chemotherapy drugs in the Western world. Lower intracellular cisplatin levels are associated with a decreased tumor response, thus cellular uptake of cisplatin is related to tumor burden. Traditional methods to assess cisplatin uptake in cells involve digesting a cell population and measuring the total platinum content. However, these approaches do not reflect the distribution and individual cellular variation of cisplatin uptake. Here, we present a new method, Single Cell Inductively Coupled Plasma-Mass Spectrometry (SC-ICP-MS), to quantitate the platinum concentration within individual cells. Experiments were performed using the A2780 cisplatin-sensitive and the corresponding cisplatin-resistant A2780-CP70 ovarian cancer cell lines. Time course experiments were performed to measure the change of cisplatin uptake over time. Individual cellular cisplatin levels were collected and a histogram representing the cell population was generated using the Syngistix Nano Application. We observed a heterogeneous distribution of cisplatin concentrations within the sample, which reflects cisplatin uptake differs from cell to cell. Other metals such as zinc, iron, and copper, were successfully analyzed at the level of a single cell by SC-ICP-MS. In conclusion, single cell ICP-MS analysis allows for the quantitation of cisplatin within individual cells. The heterogeneous distribution of cisplatin uptake more closely reflects what occurs within tumor cells. SC-ICP-MS allows for the development of strategies to increase cisplatin uptake within the tumor, translating to better clinical responses.
Scientific Focus Area: Cancer Biology
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