Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

BACKGROUND: Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. METHODS: Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. RESULTS: Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. CONCLUSIONS: These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

Clinical characteristics and treatment of unicentric retroperitoneal Castleman's disease / 中国肿瘤临床

Objective:To investigate the clinical characteristics and treatment analysis of unicentric retroperitoneal Castleman's dis-ease (CD) and to improve its levels of diagnosis and treatment. Methods:The clinical data of 18 patients with unicentric retroperitone-al CD were retrospectively reviewed from January 2002 to December 2016. We analyzed the demographic characteristics, clinical fea-tures, histological diagnosis, treatment, and prognostic characteristics of these patients. Results:The patients comprised 4 males and 14 females with a median age of 44.1 years old (ranging from 24 years old to 70 years old). The tumor was located in the kidney in one case, while it was located in the adrenal region in eight cases. In the other cases, the tumor was in the retroperitoneal region. Seven patients had a clinical atypical abdominal pain, and one patient had moderate anemia. All patients underwent surgical resection. The mean operation time was 153.3 min with a range of 60 min to 260 min. The mean blood loss was 447.2 mL (ranging from 10 mL to 3000 mL). Two cases had blood transfusion after operation, and one had urinary fistula complication. CD was confirmed by histopathol-ogy. Hyaline vascular type of CD was observed in 16 cases, and mixed type of CD was observed in 2 cases. The median follow-up was 25 months. One patient had tumor recurrence after 2 years of operation and died. Other patients remained alive without recurrence. Conclusion:Unicentric retroperitoneal CD is a rare disease that is often misdiagnosed because of the absence of specific clinical mani-festations. The final diagnosis depends on the results of a pathologic examination. Complete surgical resection offers a favorable result for unicentric retroperitoneal CD.