Calreticulin down-regulation inhibits the cell growth, invasion and cell cycle progression of human hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is one of the most frequent cancers in the world. Calreticulin(CRT) is aberrantly overexpressed in many human cancer cells. The function of CRT in HCC cells remains unclear. We attempted to investigate the effects and the underlying mechanisms of CRT down-regulation on HCC cell growth, apoptosis, cell cycle progression and invasion.

CRT was aberrantly over-expressed in HCC cell lines. CRT over-expression contributes greatly to HCC malignant behavior, likely via PI3K/Akt pathway. CRT could serve as a potential biomarker and therapeutic target for hepatocellular carcinoma.

To investigate the function of CRT in HCC cells, small interfering RNA (siRNA) was used to knock down the expression of CRT in SMMC7721 and HepG2 HCC cells. CRT expression was examined by Western blot and immunofluorescence. Cell proliferation was detected by CCK-8 assay. Cell cycle and apoptosis were measured by the flow cytometry. The invasion capability was assessed by transwell assay. The phosphorylation level of Akt was evaluated by Western blot.

Compared with human hepatic cells L02, CRT was apparently up-regulated in SMMC7721, HepG2 and Huh7 HCC cells. Down-regulation of CRT expression effectively inhibited HCC cell growth and invasion. CRT knockdown induced cell cycle arrest and the apoptosis in SMMC7721 and HepG2 cells. Furthermore, down-regulation of CRT expression significantly decreased the Akt phosphorylation. Conclusions: CRT was aberrantly over-expressed in HCC cell lines. CRT over-expression contributes greatly to HCC malignant behavior, likely via PI3K/Akt pathway. CRT could serve as a potential biomarker and therapeutic target for hepatocellular carcinoma.