Parthenolide facilitates apoptosis and reverses drug-resistance of human gastric carcinoma cells by inhibiting the STAT3 signaling pathway

Li,Hua; Lu,Hang; Lv,Meng; Wang,Qingsheng; Sun,Yuping

doi:10.3892/ol.2018.7739

Parthenolide facilitates apoptosis and reverses drug-resistance of human gastric carcinoma cells by inhibiting the STAT3 signaling pathway

Authors:
- Hua Li
- Hang Lu
- Meng Lv
- Qingsheng Wang
- Yuping Sun
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Affiliations: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
Published online on: January 8, 2018 https://doi.org/10.3892/ol.2018.7739
Pages: 3572-3579
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study, SGC‑7901/DDP cells were treated with different concentrations of parthenolide (PN) (2.5‑15 µmol/l), cisplatin (DDP) (1.25‑15 µg/ml) and PN+DDP. The proliferation inhibition rates were measured using an MTT assay, and the synergies of PN and DDP were analyzed. The effect of PN and DDP on SGC‑7901/DDP cell proliferation demonstrated a time‑ and concentration‑dependent association, and a synergy between PN and DDP was identified. DAPI staining and flow cytometry results indicated that 15 µmol/l PN significantly induced SGC‑7901/DDP apoptosis and G1 phase arrest compared with the untreated control group. Western blotting analysis results indicated that among the apoptosis‑associated proteins, there were dose‑dependent increases in the protein expression of apoptosis regulator BAX, cellular tumor antigen p53, cleaved caspase‑3 and cleaved capase‑9, and decreases in apoptosis regulator Bcl‑2 and Bcl‑xL protein expression levels. Among the cell cycle‑associated proteins, cyclin D1 expression was significantly decreased, cyclin‑dependent kinase inhibitor 1 expression was significantly increased, and signal transducer and activator of transcription 3 (STAT3) activation was inhibited. Scratch and Transwell assay results revealed that PN significantly inhibited SGC‑7901/DDP cell migration, and invasion. The present study demonstrated that PN induces SGC‑7901/DDP apoptosis, inhibits SGC‑7901/DDP proliferation, migration and invasion, and enhances the drug sensitivity of the cells to DDP. The underlying mechanisms may be associated with inhibition of the STAT3 signaling pathway and regulation of the downstream apoptotic protein and cyclin expression levels.

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