Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Abstract

Docetaxel is a front-line standard-of-care chemotherapeutic drug for the treatment of cancers. However, the underlying function and mechanism of docetaxel in human hepatocellular carcinoma (HCC) are uncertain. Therefore, the present study aimed to determine the effects of docetaxel on cell apoptosis and SOX2 expression in cultured human HCC stem cells. After human HCC stem cells were treated with docetaxel, cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) method, the cell apoptotic rate was evaluated by flow cytometry, the expression of CD133 and sex determining region Y-box 2 (SOX2) was determined by RT-PCR and immunohistochemistry, and the protein levels of CD133, SOX2, phosphoinositide 3-kinases (PI3K), AKT and phosphorylated AKT (p-AKT) were analyzed by western blotting. The results indicated that SOX2 and CD133 were highly expressed in patients with HCC while their expression was significantly decreased after patients with HCC were treated with docetaxel. In vitro, docetaxel inhibited the proliferation while it enhanced the apoptosis of human CD133-expressing HCC stem cells. Furthermore, lower expression of p-AKT and SOX2 were revealed in the presence of docetaxel. Notably, docetaxel-inhibited SOX2 expression and growth of human CD133-expressing HCC stem cells were partially restricted following the block of the PI3K/AKT signaling pathway using the inhibitor LY294002. The present study collectively indicated that docetaxel promoted apoptosis and upregulated SOX2 expression of human HCC stem cells through the suppression of the PI3K/AKT signaling pathway.

Anti-oncogenic effects of SOX2 silencing on hepatocellular carcinoma achieved by upregulating miR-222-5p-dependent CYLD via the long noncoding RNA CCAT1

“…We found increased SOX2 expression in HCC tissues in our study, which is in line with previous studies [ 14 , 15 ]. Moreover, we found that SOX2 was involved in HepG2 cell proliferation, migration, and invasion, also in agreement with a previous study [ 9 ].…”

“…Recently, SOX2 has been linked to cancer progression due to its effects on cell proliferation, invasion, and migration properties [ 10 ], with well-established involvement in prostate and cervical cancers [ 11 , 12 ], and likewise in the case of HCC development [ 13 – 15 ]. Previous work has shown that activation of the PI3K/AKT signaling pathway could up-regulate SOX2 expression of human HCC stem cells [ 14 ]. Furthermore, high SOX2 expression is associated with the prediction of poor survival in HCC patients [ 16 ].…”

Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis

“…Here, we observed that 4MU increased the pro-apoptosis genes Bax and Puma, while decreased the anti-apoptosis gene Bcl2a in Huh7. It was known that CSC CD133 is correlated with anti-apoptosis property 48,49 . However, the effect of 4MU in the epithelial mesenchymal transition (EMT), another hallmark of CSC, was unclear.…”

Conjoint analysis for hepatic carcinoma with hub genes and multi-slice spiral CT

“…Current studies demonstrate that Regorafenib, Cabozantinib, and Ramucirumab are appropriate supplements for sorafenib as second-line therapy in patients with advanced HCC who are resistant, progressive, or intolerant to sorafenib; [ 7 ] Also the increase of SRY-Box Transcription Factor 2 ( SOX2 ) gene expression is related to the occurrence and development of HCC. [ 8 ] However, more core genes associated with hepatocellular carcinoma are unknown.…”