Tumorspheres Derived from HCC Cells are Enriched with Cancer Stem Cell-like Cells and Present High Chemoresistance Dependent on the Akt Pathway
Recent evidence suggests that a small subset of cells within tumors have ‘stem cell-like’ characteristics.
However, direct proof of the population of liver CSCs remains elusive. Further research is needed to identify cells
with stem cell properties in established HCC cell lines. Our previous investigation found that tumor spheres are
essentially enriched in CSCs. We hypothesized that chemoresistance in hepatocellular carcinoma (HCC) is due to
enrichment of cancer stem cells via the PI3K/Akt pathway. We found that tumor spheres cells formed from HCC
cells contained a high percentage of CD90+ cells, and these cells were more tumorigenic and resistant to
doxorubicin (DOX), showing a higher proliferation rate and lower apoptosis rate compared to cells in monolayer
culture. Treatment with DOX and PI3K/Akt inhibitor increased apoptosis and reduced viability among cells in the
tumorspheres. The expression of p-Akt1 was upregulated in tumorsphere-forming cells treated with DOX but
downregulated upon further treatment with the PI3K/Akt inhibitor. Our results demonstrate that HCC cells in tumorspheres with cancer
stem cell properties achieve chemoresistance via the PI3K/Akt1 pathway.
Keywords: Akt pathway, cancer stem cells, chemoresistance, HCC, tumorsphere.
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