Antitumor Effect of Docetaxel in Osteosarcoma by the Inhibition of Wnt Signal Channel

Abstract

Osteosarcoma (OS) is the most common type of malignant bone tumor in adults and children. Despite the great strides in biology and medicine, the survival rate of patients with metastatic disease remains very poor. This rate has been staggering with recurrence and metastasis. In the present study, we proposed Wnt/β-catenin pathway as a key biological target for the effective treatment in OS. Wnt signaling has been reported to play important roles in osteoblastogenesis. We hypothesized that docetaxel (DTX) will effectively arrest the osteosarcoma progression by suppressing the Wnt/β-catenin pathway in OS cells. Our results show that DTX significantly inhibited the cell proliferation of U2OS and SaOS-2 cancer cells in a time-dependent and dose-dependent manner. DTX inhibited the intrinsic transcriptional activity of β-catenin/Tcf in U2OS cancer cells and SaOS-2 cancer cells. GSK-3βinhibitor (SB216763) treatment remarkably increased the β-catenin/Tcf transcriptional activities. The transcriptional activities have been increased by around ~200% due to the decrease in the degradation of β-catenin mediated through GSK-3β. Summarizing, present study clearly showed that DTX inhibited Wnt/β-catenin signalling pathways and significantly reduced the matrix metallopeptodase 9 (MMP-9) protein expressions and its activity. Taken together, our findings provide novel insight on the effect of anticancer small molecules to improve the outcomes in osteosarcoma.

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

“…Certain scholars have reported that TXT can inhibit the proliferation of OS cells and induce apoptosis, and that such inhibition is time-and dose-dependent (48,49). Combination therapy using TXT and gemcitabine (GEM) has also been reported to enhance antitumor effects (50,51).…”

Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

“…After each incubation time, the media were replaced with 2 mg/ml of MTT (Sigma) solution and incubated for 4 h in a cell culture incubator. The intracellular formed formazan crystals were solubilized using DMSO and the Absorbance measurements were performed at 570 nm by a plate reader [17,18]. The viability of ASCs in each treatments groups were calculated and reported in results.…”

Molecular pathogenesis and therapeutic strategies of human osteosarcoma

“…Aberrant signaling by Wnt can also result in increased cell proliferation and migration through both the canonical b-catenin and noncanonical pathways [34][35] . Accordingly, many research efforts have shown promise for OS therapy through inhibition of Wnt and downstream proto-oncogenes [36][37][38] . However, similar to Runx2, it appears that normal Wnt signaling is also finely tuned, with other studies demonstrating a correlation between decreased pathway activity and hypoxic chemoresistance in OS [39] .…”