Ophiopogonin B induces gastric cancer cell death by blocking the GPX4/xCT‑dependent ferroptosis pathway

Zhang,Liyi; Li,Chunlei; Zhang,Yuzhan; Zhang,Jinwen; Yang,Xiaolei

doi:10.3892/ol.2022.13224

Ophiopogonin B induces gastric cancer cell death by blocking the GPX4/xCT‑dependent ferroptosis pathway

Authors:
- Liyi Zhang
- Chunlei Li
- Yuzhan Zhang
- Jinwen Zhang
- Xiaolei Yang
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Affiliations: Department of Internal Medicine, Jiaozhou Central Hospital, Qingdao, Shandong 266300, P.R. China, Department of Cardiothoracic Surgery, Shanxian Dongda Hospital, Heze, Shandong 274300, P.R. China, Department of Laboratory Medicine, Heze Hospital of Traditional Chinese Medicine, Heze, Shandong 274000, P.R. China, Department of General Surgery, 80th Army Hospital, Weifang, Shandong 261021, P.R. China
Published online on: February 1, 2022 https://doi.org/10.3892/ol.2022.13224
Article Number: 104
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ophiopogonin B (OP‑B) is extensively applied as a treatment for pulmonary disease and is reported to suppress lung cancer. However, further study is needed to determine whether OP‑B suppresses gastric cancer (GC). The mRNA levels of prostaglandin‑endoperoxide synthase 2 (Ptgs2) and ChaC glutathione‑specific gamma‑glutamylcyclotransferase 1 (Chac1) were determined using quantitative PCR. Ptgs2 and Chac1 mRNA levels were significantly increased in GC cancer tissues compared with those of adjacent normal controls. The CCK‑8 assay revealed that OP‑B suppressed GC cell viability in a time‑ and dose‑dependent manner. The administration of OP‑B in combination with different cell death inhibitors showed that only the ferroptosis inhibitor, ferrostatin‑1 (Fer‑1), abolished the OP‑B‑induced death of both AGS and NCI‑N87 cells, but not other inhibitors. Western blot analysis indicated that OP‑B reduced the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11, xCT) but had no effects on the expression of nuclear receptor coactivator 4 (NCOA4) and ferritin heavy chain 1 (FTH1) in AGS and NCI‑N87 cells. In vivo administration of OP‑B reduced the volume and weight of AGS tumors. In addition, the expression of GPX4 and xCT was reduced in nude mice treated with OP‑B compared with control mice. In summary, results of the present study suggest that OP‑B induces ferroptosis in gastric cancer cells by blocking the GPX4/xCT system.

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