Pioglitazone as a modulator of the chemoresistance of renal cell adenocarcinoma to methotrexate

  • Authors:
    • Iwona Piątkowska‑Chmiel
    • Monika Gawrońska‑Grzywacz
    • Dorota Natorska‑Chomicka
    • Mariola Herbet
    • Marcin Sysa
    • Magdalena Iwan
    • Agnieszka Korga
    • Jarosław Dudka
  • View Affiliations

  • Published online on: January 29, 2020     https://doi.org/10.3892/or.2020.7482
  • Pages: 1019-1030
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Abstract

Kidney cancer is one of the most lethal urological malignancies associated with a high risk of mortality. Recent studies have shown that several antidiabetic drugs may limit the risk of the growth of different types of cancer. Pioglitazone (PIO) belongs to a novel class of antidiabetic drugs called thiazolidinediones (TZDs), which are commonly used in the treatment of type 2 diabetes. This drug has been demonstrated to exert an inhibitory effect on cell growth in colon, prostatic, breast and pancreatic cancer lines. The aim of the present study was to assess the inhibitory effect of PIO on the proliferation of the renal adenocarcinoma cell line 769‑P. In addition, the proapoptotic potential of combined treatment with PIO and methotrexate (MTX) was evaluated, as well as the impact of the above drugs on the cell cycle of the 769‑P cells. The present study showed that PIO efficaciously inhibited the proliferation and viability of renal cancer cells, and it induced sub‑G1 cell cycle arrest and a decrease in the number of cells in the G2 phase, which indicated cytotoxic activity. PIO also exhibited proapoptotic properties at the lowest dose applied (10 µM). Furthermore, combined therapy with PIO and MTX increased the sensitivity of tumor cells to MTX while at the same time this combined therapy did not exhibit a cytotoxic effect to normal kidney cells. In renal adenocarcinoma cells, the combination of the above cytostatic agent at the lowest dose administered (MTX, 5 µM) with the peroxisome proliferator‑activated receptor γ agonist PIO exhibited better efficacy in triggering the process of apoptosis than that displayed by MTX alone.

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March 2020
Volume 43 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Piątkowska‑Chmiel, I., Gawrońska‑Grzywacz, M., Natorska‑Chomicka, D., Herbet, M., Sysa, M., Iwan, M. ... Dudka, J. (2020). Pioglitazone as a modulator of the chemoresistance of renal cell adenocarcinoma to methotrexate. Oncology Reports, 43, 1019-1030. https://doi.org/10.3892/or.2020.7482
MLA
Piątkowska‑Chmiel, I., Gawrońska‑Grzywacz, M., Natorska‑Chomicka, D., Herbet, M., Sysa, M., Iwan, M., Korga, A., Dudka, J."Pioglitazone as a modulator of the chemoresistance of renal cell adenocarcinoma to methotrexate". Oncology Reports 43.3 (2020): 1019-1030.
Chicago
Piątkowska‑Chmiel, I., Gawrońska‑Grzywacz, M., Natorska‑Chomicka, D., Herbet, M., Sysa, M., Iwan, M., Korga, A., Dudka, J."Pioglitazone as a modulator of the chemoresistance of renal cell adenocarcinoma to methotrexate". Oncology Reports 43, no. 3 (2020): 1019-1030. https://doi.org/10.3892/or.2020.7482