The effects of Livin shRNA on the response to cisplatin in HepG2 cells

Abstract

Abstract. Hepatocellular carcinoma is a lethal malignancy with poor prognosis, partially due to tumor metastasis, recurrence and resistance to chemo-or radio-therapy. Cisplatin can inhibit cancer cell DNA replication, and is widely used in the clinical treatment of tumors. The present study aimed to generate eukaryotic expression vectors for Livin shRNA and to examine the effects of Livin shRNA on the chemosensitivity of HepG2 hepatocellular carcinoma cells. Eukaryotic expression vectors for Livin shRNA (pSD11-U6/Neo/GFP/Livin) were designed and constructed. The HepG2 hepatocellular carcinoma cell line was transfected with this vector using the liposome method. The expression levels of Livin mRNA and protein were measured by quantitative polymerase chain reaction and western blot analysis. The rate of cell growth inhibition was measured using MTT assay following treatment of the cells with cisplatin (2.0 mg/l). DNA sequencing confirmed that the construction of the eukaryotic expression vector for Livin shRNA had been successful. Transfection of these vectors into HepG2 cells led to a significant reduction in the expression levels of Livin mRNA and protein (P<0.05). Cisplatin treatment was associated with significantly higher rates of cell growth inhibition in HepG2 cells transfected with Livin shRNA compared with those that were not transfected (P<0.05). The vectors constructed in the present study produced effective inhibition of the Livin gene in HepG2 cells and increased the chemosensitivity of hepatocellular carcinoma cells.

Livin enhances chemoresistance in head and neck squamous cell carcinoma

“…Therefore, in the present study, we investigated the role of Livin in determining susceptibility to commonly used chemotherapeutic drugs, such as docetaxel, cisplatin and 5-FU, in human HNSCC cell lines. Although several studies have described that Livin contribute to the resistance of various chemotherapeutic drugs including cisplatin in various cancers (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), the present study is the first to demonstrate the correlation between Livin and chemoresistance in human HNSCC.…”

“…Livin, a recently discovered IAP, is composed of a single BIR domain and a RING motif (9). Livin has been implicated in chemoresistance in various cancers (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). It has been reported to play a role in resistance to cisplatin in bladder cancer, renal carcinoma, gastic cancer, hepatocellular carcinoma, lung adenocarcinoma/ non-small cell carcinoma, osteosarcoma, colon cancer and ovarian carcinoma (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)31).…”

Silencing thelivingene enhances the cytotoxic effects of anticancer drugs on colon cancer cells

“…In other studies, silencing of livin reduced drug resistance to chemotherapy in glioblastoma, melanoma, and lung cancer [121314]. In addition, several studies have reported a synergetic anticancer effect when silencing of the livin gene is combined with chemotherapy [1516171819]. …”

The role of Livin expression in the clinicopathological features and prognosis of lung cancer: a meta-analysis

“…In our assessment of outcome stability by sensitivity analyses, when a single study was removed, there were no significant changes of pooled OR, indicating that the results were consolidated. Significant association between Livin expression and lung cancer prognosis may be attributed to the binding between the BIR domain of Livin and caspase-3, 7 and 9, a process which inhibits caspase activity and blocks the apoptosis signal transduction of tumor cells ( 48 ). Alternatively, Livin may bind TAB1 to mediate the activation of JNK1 through TAB1 activation, a process which inhibits cell apoptosis ( 49 ) and subsequently causes tumor cell to metastasis and invasiveness.…”