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. 2015 Jul 11;6(27):23561–23581. doi: 10.18632/oncotarget.4452

Figure 7. Sensitization of colon cancer cells to a long-term suboptimal dose of 5-fluorouracil exposure when combined with VTD.

Figure 7

A–D. (A) HCT-116, (B) LoVo, (C) SW-480, and (D) U2OS were treated with VTD (10–300 μM) for 10 days. Colony formation assays showed VTD effectively reduces cell viability in a cell type-dependent manner. E–G. (E) HCT-116, (F) LoVo, and (G) U-2OS were treated with suboptimal doses of 5-FU and VTD (50 and 100 μM) for 10 days. Clonogenic survival assays revealed an intermediate-dose of VTD significantly potentiates the standard chemotherapy used at very low dose (1–5 μM 5-FU). H–I. A series of flow cytometry assays using an antibody against the CD44 cancer stem cell marker illustrated that VTD can target CD44+ cancer stem cells and eventually eliminate them in a dose-dependent manner, implicating VTD as a potential cancer stem cell-targeting therapy. J. Tumor tissue lysates from 48 patients with colon cancer alongside the matched adjacent normal colon tissue lysates were probed with anti-UBXN2A and anti-Actin antibodies, followed by quantitation and normalization of signals. UBXN2A expression shows a marked downregulation in ≥ 50% of patients with colon cancer. UBXN2A expression levels may have a correlation with the stages of colon cancer as several patients at stage III had low level of UBXN2A (inset). (I) The proposed mechanism action of VTD. VTD increases the expression of UBXN2A, which releases the p53 from mot-2′s sequestration and, together with standard chemotherapy, can cause an effective tumor suppression.