Luteolin potentiates low‑dose oxaliplatin‑induced inhibitory effects on cell proliferation in gastric cancer by inducing G2/M cell cycle arrest and apoptosis

Ma,Jun; Chen,Xiaojie; Zhu,Xuejie; Pan,Zhaohai; Hao,Wenjin; Li,Defang; Zheng,Qiusheng; Tang,Xuexi

doi:10.3892/ol.2021.13134

Luteolin potentiates low‑dose oxaliplatin‑induced inhibitory effects on cell proliferation in gastric cancer by inducing G2/M cell cycle arrest and apoptosis

Authors:
- Jun Ma
- Xiaojie Chen
- Xuejie Zhu
- Zhaohai Pan
- Wenjin Hao
- Defang Li
- Qiusheng Zheng
- Xuexi Tang
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Affiliations: College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266003, P.R. China, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, School of Life Sciences, Nantong University, Nantong, Jiangsu 226000, P.R. China
Published online on: November 12, 2021 https://doi.org/10.3892/ol.2021.13134
Article Number: 16
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although the reduction of oxaliplatin doses may alleviate deleterious side effects of gastrointestinal and gynecological cancer treatment, it also limits the anticancer therapeutic effects. As a high‑efficient and low‑priced herbal medicine ingredient, luteolin is an agent with a broad spectrum of anticancer activities and acts as a potential enhancer of therapeutic effects of chemotherapy agents in cancer treatment. This study focused on the antitumor effects and mechanism of combined treatment with luteolin and oxaliplatin on a mouse forestomach carcinoma (MFC) cell line. The study used CCK‑8 assay, flow cytometry, Annexin V‑FITC/PI double staining assay, reactive oxygen species testing assay, mitochondrial membrane potential testing assay, and western blot assay. The results showed that luteolin and oxaliplatin exerted synergistic effects on inhibiting MFC cell proliferation by inducing G₂/M cell cycle arrest and apoptosis. Inhibiting the tumor necrosis factor receptor‑associated protein 1/phosphorylated‑extracellular‑regulated protein kinases1/2/cell division cycle 25 homolog C/cyclin‑dependent kinase‑1/cyclin B1 pathway was indispensable to the combined treatment with luteolin and oxaliplatin to induce G2/M cell cycle arrest. In addition, luteolin increased oxidative stress in MFC cells treated with a low dose of oxaliplatin. The combined therapy damaged mitochondrial membrane potential and regulated BCL‑2‑associated X protein and B‑cell lymphoma 2 protein expression, leading to apoptosis. Findings of the present study suggest that luteolin may be a qualified chemotherapy enhancer to potentiate the anticancer effects of low‑dose oxaliplatin in MFC cells. This work provides a theoretical foundation for future research on applications of luteolin in clinical chemotherapy.

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