Banxia xiexin decoction affects drug sensitivity in gastric cancer cells by regulating MGMT expression via IL‑6/JAK/STAT3‑mediated PD‑L1 activity

Feng,Xuan; Xue,Feng; He,Guihua; Ni,Qing; Huang,Suiping

doi:10.3892/ijmm.2021.4998

Banxia xiexin decoction affects drug sensitivity in gastric cancer cells by regulating MGMT expression via IL‑6/JAK/STAT3‑mediated PD‑L1 activity

Authors:
- Xuan Feng
- Feng Xue
- Guihua He
- Qing Ni
- Suiping Huang
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Affiliations: Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
Published online on: July 5, 2021 https://doi.org/10.3892/ijmm.2021.4998
Article Number: 165
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Banxia xiexin decoction (BXXX) is a classic preparation used to treat gastrointestinal diseases, and also has certain therapeutic effects on gastrointestinal tumors. BXXX has been reported to regulate the expression of proteins associated with drug resistance and sensitivity in tumors, and thus, the aim of the present study was to investigate the mechanisms of BXXX drug sensitivity in gastric cancer (GC). The expression levels of programmed cell death 1 ligand 1 (PD‑L1), 6‑O‑methylguanine‑DNA methyltransferase (MGMT) and STAT3 were immunohistochemically detected in the cancer and adjacent non‑cancer tissues of patients with GC, and in vitro experimentation was conducted using drug‑resistant and ‑sensitive GC cells. The expression levels of PD‑L1, MGMT and STAT3 were determined using reverse transcription‑quantitative PCR. Different concentrations of BXXX drug serum were used to treat the cells and the cellular inhibition rate was assessed using a Cell Counting Kit‑8 assay. Flow cytometry was used to detect apoptosis, and western blot analysis was used to detect the expression levels of IL‑6, IFN‑γ, JAK/STAT3 pathway proteins, PD‑L1 and MGMT. The association between PD‑L1 and MGMT protein expression levels was subsequently assessed via co‑immunoprecipitation. Furthermore, in vivo studies were conducted following the establishment of a drug‑resistant tumor‑bearing mouse model, where GC tumor size was assessed under different treatment conditions, and western blot analysis was used to detect the expression of related pathway proteins. The expression levels of PD‑L1, MGMT and STAT3 were significantly increased in GC tissues, GC cells and cisplatin‑resistant cells. Furthermore, BXXX inhibited the proliferation of drug‑resistant cells and promoted the inhibitory effects of chemotherapeutic drugs on drug‑resistant cells. BXXX also inhibited the expression levels of IL‑6, IFN‑γ and JAK/STAT3 pathway proteins, as well as the expression levels of PD‑L1 and MGMT. Colivelin, an activator of STAT3, reversed the effects of BXXX on drug‑resistant GC cells, and significantly reversed the effect of BXXX on PD‑L1 expression. In conclusion, BXXX was found to influence the drug sensitivity of GC cells by regulating the expression of MGMT. This process functions viaPD‑L1, which was itself mediated by IL‑6/JAK/STAT3 signaling.

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