Objective: Rhabdomyosarcoma, a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens and radiation, outcomes remain poor, especially in advanced disease. A novel... [ view full abstract ]
Objective: Rhabdomyosarcoma, a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens and radiation, outcomes remain poor, especially in advanced disease. A novel retinoid, 9-cis-UAB30 (UAB30), has been developed that has virtually no toxicity. We hypothesized that treatment with UAB30 would induce cell cycle arrest, inhibit cellular migration and invasion, and lead to apoptosis and cell death in rhabdomyosarcoma cell lines.
Methods: The human rhabdomyosarcoma cell lines SJCRH30 and RD were utilized. AlamarBlue® and trypan blue exclusion was used to measure cell survival and proliferation, respectively. Cell cycle analysis was completed with flow cytometry. Migration and invasion assays were performed with Transwell plates and scratch assays. Apoptosis was detected via caspase 3 activity by a colorimetric assay.
Results: The following results were noted in both cell lines treated with increasing concentrations of UAB30: a) cell cycle arrest with a significant increase in the percentage of cells in G1 and a decrease in S phases; b) a significant decrease in cellular migration and invasion; c) a significant decrease in cellular proliferation; and d) a significant decrease in cell survival. Further, increased caspase 3 cleavage confirmed that cell death was due to apoptosis.
Conclusions: The synthetic retinoid, 9-cis-UAB30, had a significant impact upon rhabdomyosarcoma cell lines resulting in cell cycle arrest, decreased proliferation, migration and invasion, and increased apoptosis. These results suggest a potential therapeutic role for UAB30 in rhabdomyosarcoma treatment.
