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 type2 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‑Pcells. The present study showed that PIO efficaciously inhibited the proliferation and viability of renal cancer cells, and it induced sub‑G1cell cycle arrest and a decrease in the number of cells in the G2phase, which indicated cytotoxic activity. PIO also exhibited proapoptotic properties at the lowest dose applied (10µM). 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, 5µM) with the peroxisome proliferator‑activated receptorγ agonist PIO exhibited better efficacy in triggering the process of apoptosis than that displayed by MTX alone.
Highlights
Cancer is one of the most common causes of death and a major health concern worldwide [1]
The 24‐h treatment of cancer cells with MTX (5 and 10 μM) did not cause significant growth inhibition in 769‐P cells, contrary to the observations in the normal cell line Vero (Fig. 1A and B, respectively). These results confirm the resistance of renal adenocarcinoma cells to antifolates
It was demonstrated that the viability of 769‐P cells was used. 769‐P and Vero cells grew as a monolayer with typical epithelioid cobblestone morphology (Figs. 2A‐D and 3A‐D)
Summary
Cancer is one of the most common causes of death and a major health concern worldwide [1]. Effective treatment of patients remains a real and serious challenge in oncology. Conventional therapeutic methods, including chemotherapy, radiotherapy and surgery, often are not sufficiently effective or have a high risk of adverse effects for patients [1,2]. Renal cell carcinoma (RCC), called renal adenocarcinoma, remains one of the most lethal urological malignancies in the world, and is associated with a high resistance to conventional therapy. Recent epidemiologic studies have shown that patients with diabetes (mainly type 2) may be predisposed to develop nephropathy and several malignancies, including kidney cancer, when compared with the general population [9,10,11,12,13,14,15,16,17]
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