AIMTo study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DU145 cancer cells.

METHODSDU145, an androgen-independent human prostate cancer cell line, was used in the experiment. Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting.

RESULTSClonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. Twenty-four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein, especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DU145 cells at G2/M phase. This G2/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1 and less dramatically cdc-2, but stably elevated p21 cip1 levels with increasing genistein concentrations.

CONCLUSIONGenistein enhanced the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair.

Androgens ; physiology ; Anticarcinogenic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; DNA, Neoplasm ; analysis ; biosynthesis ; genetics ; Flow Cytometry ; Genistein ; pharmacology ; Humans ; Immunoblotting ; In Situ Nick-End Labeling ; Male ; Prostatic Neoplasms ; drug therapy ; radiotherapy ; Tumor Stem Cell Assay

Objective: Primary undifferentiated pleomorphic sarcoma (UPS) of the bone is rare. However, the common sites are the knee and proximal femur and humerus, while spinal involvement is rare. We report a case of primary UPS of the 11th thoracic vertebra, where corpectomy would have been difficult and extensive, treated with carbon ion radiotherapy.Case report: A 76-year-old man presented with an osteolytic tumor of the 11th thoracic vertebra on plain computed tomography (CT). The spinal cord was compressed and displaced posteriorly by the tumor on magnetic resonance imaging (MRI), and extraosseous extension was observed. An incisional biopsy was performed, and primary UPS of the 11th thoracic vertebra was diagnosed pathologically. Total en bloc spondylectomy was considered to be challenging because of the extraosseous extension and the patient’s age; thus, carbon ion radiotherapy (70.4 GyE / 32 fraction) was performed. Denosumab (120 mg) was administered subcutaneously every four weeks. No adjuvant chemotherapy was administered. Four years post-treatment, imaging revealed a compression fracture of the 11th thoracic vertebra, but there was no recurrence.Conclusion: Despite a poor prognosis and an aggressive course of UPS of the spine, the tumor continues to be controlled without local recurrence four years after carbon ion radiotherapy.