Abstract
The multireceptor tyrosine kinase inhibitor sorafenib is a Food and Drug Administration-approved first-line drug for the treatment of advanced liver cancer that can reportedly extend overall survival in patients with advanced hepatocellular carcinoma (HCC). Primary and acquired resistance to sorafenib are gradually increasing however, leading to failure of HCC treatment with sorafenib. It is therefore crucial to study the potential mechanism of sorafenib resistance. The results of the current study indicate that neurite outgrowth inhibitor protein B receptor (NgBR) is overexpressed in cultured sorafenib-resistant cells, and that its expression is negatively correlated with the sensitivity of liver cancer cells to sorafenib. Artesunate can inhibit the expression of NgBR, and it may block sorafenib resistance. Herein we report that sorafenib treatment in combination with artesunate overcomes HCC resistance to sorafenib alone in a cell culture model.
Highlights
Hepatocellular carcinoma (HCC) is a primary solid tumor that develops chemoresistance
The results of the current study indicate that neurite outgrowth inhibitor protein B receptor (NgBR) is overexpressed in cultured sorafenib-resistant cells, and that its expression is negatively correlated with the sensitivity of liver cancer cells to sorafenib
Our results show that artesunate can inhibit NgBR expression, and in combination sorafenib artesunate can overcome the resistance to sorafenib in hepatocellular carcinoma cells
Summary
Hepatocellular carcinoma (HCC) is a primary solid tumor that develops chemoresistance. This limits the number of effective interventions for advanced HCC, leading to over 700,000 deaths annually around the world (Fukui et al, 2018). The successful development of molecularly targeted drugs has reportedly extended the overall survival of patients with chronic liver cancer (Al-Salama et al, 2019). The multityrosine kinase inhibitor sorafenib was the first small-molecule-targeted drug that demonstrably extended the overall survival of advanced HCC patients (Gramantieri et al, 2020). Most patients with advanced HCC develop resistance to sorafenib early during treatment, and do not benefit from it in the long term (Zhang et al, 2020). MAPK14 activation in HCC cells was associated with no response to sorafenib in a murine model of tumor development and treatment
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