Reduction of PKCα decreases cell proliferation, migration, and invasion of human malignant hepatocellular carcinoma

Protein kinase C (PKC) superfamily play key regulatory roles on the development of cancer. However, the exact role of these enzymes in human hepatocellular carcinoma (HCC) has not been well established. Using the RT-PCR and Western blotting to analyze the levels of PKC isoforms mRNA and protein in the five different differentiated hepatoma cell lines, we found that PKCα was highly expressed in the poor-differentiated HCC cell lines (SK-Hep-1 and HA22T/VGH) as compared with that in the well-differentiated HCC cell lines (PLC/PRF/5, Hep3B, and HepG2). When treated with PKCα antisense oligonucleotides (ODN), both HA22T/VGH and SK-Hep-1 cells lines showed the reduction of PKCα expression, as well as a deceleration in the growth rate and in the level of cyclin D1, but the increase in the levels of p53 and p21WAF1/CIP1. Moreover, the reduction of PKCα expression also inhibited the migratory and invasive potential of both HA22T/VGH and SK-Hep-1 cells lines, and revealed a down-regulation of several migration/invasion- related genes (MMP-1, u-PA, u-PAR, and FAK). These phenomenon were also confirmed by DNA-based small interfering RNA (siRNA) PKCα and PKCα/β specific inhibitor Go6976. Thus, the results indicated that PKCα may be associated with regulation of cell proliferation/migration/ invasion in human poorly differentiated HCC cells, suggesting a role for the PKCα in the malignant progression of human HCC.