NLRP3 inflammasome activation By 17 beta-estradiol is a potential therapeutic target in hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it mostly arises as a consequence of persistent chronic inflammation. Recently, NLRP3 inflammasome has caught the attention of many research groups due to its involvement in different types of cancer. However, its direct role in HCC remains elusive. Our study aimed to evaluate the role of NLRP3 inflammasome and pyroptosis in HCC and to clarify the potential mechanism by which 17 beta-estradiol (E2) can be used as a protective factor against HCC. NLRP3, caspase-1 (CASP1) as well as gasdermin-D (GSDMD) mRNA expression levels were assessed in human HCC tissues and adjacent non-cancerous liver tissues. Also, HepG2 HCC cells were cultured and treated with E2, followed by detection of the mRNA levels of these three genes. Our results revealed that NLRP3, CASP1, and GSDMD mRNA expressions were significantly lower in HCC tissues than in controls, and this under-expression was closely correlated with advanced HCC stages and grades. In contrast, HepG2 HCC cells displayed significantly higher expression levels of NLRP3 inflammasome components and GSDMD in the two E2-treated groups compared to the untreated group. Also, NLRP3, CASP1, and GSDMD mRNA expression levels were positively correlated with each other. This study confirmed that lack of NLRP3 inflammasome is involved in HCC progression and 17 beta-estradiol-induced activation of NLRP3 inflammasome may be effective in HCC treatment as it inhibited tumor cell growth and proliferation by triggering CASP1-dependent pyroptosis in HCC cells.

Automated summary

This study aimed to evaluate the role of NLRP3 inflammasome and pyroptosis in hepatocellular carcinoma (HCC) and to clarify the potential mechanism of 17-beta-estradiol (E2) as a protective factor against HCC. The results showed that NLRP3 inflammasome expression was lower in HCC tissues and higher in E2-treated HCC cells. Lack of NLRP3 inflammasome was involved in HCC progression, and E2-induced activation of NLRP3 inflammasome inhibited tumor cell growth and proliferation through CASP1-dependent pyroptosis in HCC cells.