Itraconazole inhibits the proliferation of gastric cancer cells in vitro and improves patient survival

Lan,Ke; Yan,Ron; Zhu,Kun; Li,Wenhan; Xu,Zisen; Dang,Chengxue; Li,Kang

doi:10.3892/ol.2018.9072

Itraconazole inhibits the proliferation of gastric cancer cells in vitro and improves patient survival

Authors:
- Ke Lan
- Ron Yan
- Kun Zhu
- Wenhan Li
- Zisen Xu
- Chengxue Dang
- Kang Li
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Affiliations: Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China
Published online on: July 4, 2018 https://doi.org/10.3892/ol.2018.9072
Pages: 3651-3657
Copyright: © Lan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Itraconazole is a Food and Drug Administration‑approved antifungal drug belonging to the azole family. Recent studies reported that itraconazole has potential anticancer activity. Whether combining itraconazole with other anticancer compounds such as 5‑fluorouracil (5‑FU), a potent drug used in the treatment of gastric cancer, is unknown and warrants further study. In the present study, SGC‑7901 gastric cancer cells were chosen to assess the anticancer effects of itraconazole in combination with 5‑FU. Cell proliferation was assessed by a Cell Counting Kit‑8 assay, and apoptosis was assessed by Annexin V/propidium iodide (PI) staining and flow cytometry. Cell cycle distribution was determined by PI staining and flow cytometer. Single‑cell gel electrophoresis was used to estimate DNA damage. Medical records of patients with gastric cancer were retrospectively reviewed, and the patients treated with itraconazole were selected for the present study. Itraconazole treatment inhibited the proliferation and altered cell cycle in SGC‑7901 cells while promoting early apoptosis and DNA damage. These effects were promoted in cells treated with both itraconazole and 5‑FU. Combination itraconazole and 5‑FU treatment showed a synergetic anticancer effect in SGC‑7901 cells. In vivo, itraconazole was able to improve the outcome of 5‑FU‑based chemotherapy. Itraconazole alone and in combination with 5‑FU was able to inhibit the growth of gastric cancer in vitro, and it was able to prolong the survival of patients with gastric cancer.

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