AI Article Synopsis

  • Researchers created reprogrammed H460 cancer cells (R-H460) to study how epigenetic changes contribute to drug resistance against treatments like cisplatin and paclitaxel.
  • After differentiating these cells for different time periods, they found that cells differentiated for 13 days (13dR-H460) developed short-term drug resistance, while those differentiated for 40 days (40dR-H460) lost that resistance.
  • This study indicates that the mechanisms behind short-term and medium-term drug resistance could lead to new approaches in cancer treatment by targeting the epigenetic changes in cells.

Article Abstract

To elucidate the epigenetic mechanisms of drug resistance, epigenetically reprogrammed H460 cancer cells (R-H460) were established by the transient introduction of reprogramming factors. Then, the R-H460 cells were induced to differentiate by the withdrawal of stem cell media for various durations, which resulted in differentiated R-H460 cells (dR-H460). Notably, dR-H460 cells differentiated for 13 days (13dR-H460 cells) formed a significantly greater number of colonies showing drug resistance to both cisplatin and paclitaxel, whereas the dR-H460 cells differentiated for 40 days (40dR-H460 cells) lost drug resistance; this suggests that 13dR-cancer cells present short-term resistance (less than a month). Similarly, increased drug resistance to both cisplatin and paclitaxel was observed in another R-cancer cell model prepared from N87 cells. The resistant phenotype of the cisplatin-resistant (CR) colonies obtained through cisplatin treatment was maintained for 2-3 months after drug treatment, suggesting that drug treatment transforms cells with short-term resistance into cells with medium-term resistance. In single-cell analyses, heterogeneity was not found to increase in 13dR-H460 cells, suggesting that cancer cells with short-term resistance, rather than heterogeneous cells, may confer epigenetically driven drug resistance in our reprogrammed cancer model. The epigenetically driven short-term and medium-term drug resistance mechanisms could provide new cancer-fighting strategies involving the control of cancer cells during epigenetic transition.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080688PMC
http://dx.doi.org/10.1038/s12276-020-0464-3DOI Listing

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