Taurolidine promotes cell apoptosis by enhancing GRIM‑19 expression in liver cancer

Li,Feifei; Qi,Jianni; Qin,Chengyong; Fu,Zhaoqing; Ren,Wanhua

doi:10.3892/or.2018.6711

Taurolidine promotes cell apoptosis by enhancing GRIM‑19 expression in liver cancer

Authors:
- Feifei Li
- Jianni Qi
- Chengyong Qin
- Zhaoqing Fu
- Wanhua Ren
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Affiliations: Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong 250021, P.R. China, Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Thoracic Surgery, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong 250014, P.R. China
Published online on: September 18, 2018 https://doi.org/10.3892/or.2018.6711
Pages: 3743-3751

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Abstract

Taurolidine (TRD) is a substance derived from the amino sulfonic acid taurine, which was originally used to treat peritonitis and catheter‑associated bloodstream infections, due to its antimicrobial and anti‑inflammatory properties. A recent study reported the anticancer function of TRD in malignant tumors; however, the effects and mechanisms of TRD in liver cancer remain unclear. The present study aimed to investigate the effects and mechanism of TRD treatment on human liver cancer cells. The viability and apoptosis of liver cancer cells were evaluated using the MTT assay and flow cytometry. Subsequently, small interfering RNA (siRNA) was used to knock down the expression of gene associated with retinoid‑interferon‑induced mortality‑19 (GRIM‑19), after which, reverse transcription‑quantitative polymerase chain reaction was used to detect the mRNA expression levels of GRIM‑19, whereas immunofluorescence was used to analyze the location of GRIM‑19. Furthermore, western blotting was performed to detect the protein expression levels of GRIM‑19, cyclin D1, signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)‑STAT3, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax). The STAT3 pathway was inhibited using niclosamide. The results revealed that TRD reduced the viability of liver cancer cells and induced apoptosis at higher frequencies. In addition, the expression levels of GRIM‑19 were increased in a time‑ and dose‑dependent manner following TRD treatment. Alongside GRIM‑19 upregulation, the expression levels of Bax were increased, whereas those of cyclin D1, Bcl‑2 and p‑STAT3 were decreased. Furthermore, following GRIM‑19 knockdown, the effects of TRD on the viability and apoptosis of HepG2 cells, and the expression of downstream target genes (including cyclin D1, STAT3, p‑STAT3, Bcl‑2 and Bax) were reversed. Conversely, treatment with a p‑STAT3 inhibitor had an inverse effect on the expression of these genes but did not affect GRIM‑19 expression compared with the TRD group. These results indicated that TRD may contribute to cell apoptosis by inducing GRIM‑19 expression and deactivating the STAT3 signaling pathway in liver cancer cells.

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