HBV suppresses thapsigargin-induced apoptosis via inhibiting CHOP expression in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) accounts for a proportion of cancer-associated mortalities worldwide. Hepatitis B virus (HBV) infection is a major cause of HCC in China. Thapsigargin (TG) is a potential antitumor prodrug, eliciting endoplasmic reticulum (ER) stress via the inhibition of the ER calcium pump, effectively inducing apoptosis. The present study therefore examined the role of HBV in TG-induced apoptosis using two HCC cell lines, HBV positive HepG2.2.15 and HBV negative HepG2. When these two cell lines were treated with TG, HepG2.2.15 was less susceptible to apoptosis than HepG2. This phenomenon was confirmed by an MTT assay and Annexin V-FITC/propidium iodide staining. Reverse transcription quantitative polymerase chain reaction and western blotting were used to detect the expression levels of genes in the ER stress pathway subsequent to treatment with TG. Notably, the mRNA and protein levels of the apoptosis factor DNA damage inducible transcript 3 (CHOP) increased significantly in the HepG2 cells compared with the HepG2.2.15 cells. Additionally, the HepG2.2.15 cells treated with interferon-α exhibited higher levels of CHOP compared with the untreated cells. The overexpression or knockdown of CHOP microRNA in HepG2.2.15 or HepG2 cells may reduce the difference in apoptosis status between the two cell lines. These results suggest that HBV may inhibit the apoptosis induced by ER stress. These findings may be useful in the development of selective therapies for patients with HBV-positive tumors.