Abstract
The Notch pathway plays an important role in both stem cell biology and cancer. Notch2 was reported to be upregulated in human hepatocellular carcinoma (HCC) tissues. However, the biological function of Notch2 in human HCC cells has not yet been documented. The aim of this study was to investigate its possible function on the progression of human HCC cells. The expression of Notch2 was detected in four human HCC cell lines by western blotting. Next, Notch2 was knocked down by small interference RNA (siRNA) in human HCC cells. The role of Notch2 in human HCC cells was investigated by cell proliferation assay, colony formation assay, chemoresistance and xenograft formation assay. In the present study, western blotting revealed that the expression of Notch2 was upregulated in human HCC cell lines. Genetic depletion of Notch2 in HCC cells not only resulted in significantly inhibited proliferation, cell cycle progression and colony formation ability but also increased its sensitivity to 5-fluorouracil (5-FU) compared with controls. In addition, upregulation of Notch2 was discovered in CD90 positive HCC cells, CD90 is a marker of hepatic stem cells. Most importantly, knockdown of Notch2 in HCC cells impaired the tumor formation invivo. Taken together, our findings indicate that Notch2 may confer stemness properties in HCC; downregulation of Notch2 inhibited the proliferation and tumor formation of HCC cells and increase their sensitivity to 5-FU, suggesting Notch2 as a potential therapeutic target for HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most prevalent carcinomas and the third leading cause of cancer-related deaths throughout the world [1]
The Notch pathway is one of several key pathways linked to both stem cell biology and cancer [8]
To investigate the possible role of Notch2 on HepG2 and SMMC-7721 cells, we employed RNAi to deplete its expression in these cells, both of which were treated with NC-small interference RNA (siRNA) or Notch2-siRNA
Summary
Hepatocellular carcinoma (HCC) is one of the most prevalent carcinomas and the third leading cause of cancer-related deaths throughout the world [1]. The best curative procedures for patients with HCC are hepatectomy and liver transplantation. Curative therapies are not effective in a large number of patients due to diagnosis at advanced stage [2]. In recent years, compelling evidence has emerged in support of the presence of cancer stem-like features that is responsible for chemoresistance and recurrence of HCC [4,5,6,7]. The Notch pathway is one of several key pathways linked to both stem cell biology and cancer [8]. Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer stem-like side population cells [15]. Since aberrant Notch signaling has been implicated in cancer and cancer stem cell therapeutic strategies that effectively target Notch signaling could have a major impact on cancer patient survival
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