TDK conference 2024

The use of platinum derivatives in the treatment of various cancers has a history going back several decades. However, the clinical use of these drugs is seriously hampered by toxicity due to accumulation in healthy cells and resistance by some cancer cells. Previous research has successfully investigated the cell transport mechanisms, antineoplastic effects and toxicity of cisplatin and carboplatin, but quantifying platinum uptake by individual cells was technologically challenging until a few years ago. The SC-ICP-MS method used in the present research may provide a solution to these problems.

Two murine carcinoma cell lines, C26 (colorectal carcinoma) and 4T1 (mammary carcinoma), and a healthy epithelial cell line from a canine kidney, MDCK, were used in the experiments. The cell cultures were exposed to different concentrations of cisplatin and carboplatin (10, 20 and 40 μM) for 24 h, washed three times and centrifuged. Morphological changes in cell cultures were monitored using an Olympus IX70 inverse phase-contrast microscope, while cell counts were measured with a Merck ScepterTM 3.0 cell counter. The cellular uptake and intercellular distribution of platinum complexes were measured using a Perkin Elmer NexION2000.

While evaluating the results, we found that different cell lines exposed to the same concentrations of platinum complexes take up platinum to different extents, and higher drug concentrations increased the amount of platinum measured within the cells. This latter relationship was directly proportional for several cell lines over certain concentration ranges. In cisplatin-treated cells, platinum reached higher concentrations and was taken up by more cells than in carboplatin-treated cells. Additionally, significant cell death was observed in cultures of all cell lines when the exposure surpassed a certain concentration, leading to cell fragmentation. This was detected by SC-ICP-MS as an increase in cell number. The exposure level that induced this phenomenon was greater in 4T1 and MDCK than in C26, demonstrating the greater resistance of these cell lines to the cytotoxic effects of platinum. No morphological lesions were observed in carboplatin-treated cultures, and the presence of fragmentation was not demonstrated. This indicates that the cell-damaging effect of cisplatin is greater than that of carboplatin at the same concentrations. Our results support the findings of several previous studies and the clinical experience with the agents in question.