Abstract
Pyroptosis is a caspase-1 dependent programmed cell death, which is involved in the pathologic process of several kinds of cancers. Loss of caspase-1 gene expression has been observed in prostate and gastric cancers. However, the role of pyroptosis in human hepatocellular carcinoma (HCC) remains largely unknown. The aim of this study was to investigate the involvement of pyroptosis in the pathogenesis of HCC. Our study showed that pyroptosis was inhibited in HCC tissues and cells. Administration of berberine inhibited the viability, migration and invasion capacity of HepG2 cells through the induction of pyroptosis both in vitro and in vivo, which was attenuated by caspase-1 inhibitor Ac-YVAD-CMK. Conclusively, pyroptosis is involved in the pathogenesis of HCC, and may be a new neoplastic target for the treatment of HCC.
Highlights
Liver cancer is the second-commonest cause of cancer related death, and accounted for 746,000 world deaths in 2012 [1]
The results showed that caspase-1 mRNA and protein levels were downregulated in hepatocellular carcinoma (HCC) tissues relative to adjacent normal tissues (Figure 1B & 1C)
A similar phenomenon was observed in HCC and hepatocyte cell lines: the expression of caspase-1 in Bel7402 and HepG2 cells was lower than that in HL-7702 (Figure 1D,E & 1F)
Summary
Liver cancer is the second-commonest cause of cancer related death, and accounted for 746,000 world deaths in 2012 [1]. Human hepatocellular carcinoma (HCC) arises from hepatocytes and represents the most frequent type of primary liver cancers. A large amount of genomic and epigenetic alterations has been identified, mainly focused on apoptosis, autophagy and hepatitis virus, the treatment of HCC is still a conundrum [2,3,4]. Activation of caspase-1 distinguishes pyroptosis from other kinds of cell death. In this process, cells recognize certain harmful signals, produce cytokines, swell, burst, and die [5]. The activation of pyroptosis may promote cell death and exert anticancer properties. The loss of caspase-1 gene expression was found in human prostate cancer [9, 10]. Little is known regarding the role of pyroptosis in HCC
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