Regulation of chondrosarcoma cell growth using synthesized hydrogels with different electric charges / 生物医学工程学杂志

To develop standard in vitro chondrosarcoma models, we synthesized three hydrogels (i. e., PDMAAm, PNaAMPS and PMETAC) and investigated the influence of Young's modulus, swelling ratio and electric charges on the behavior of chondrosarcoma cells seeded on the hydrogels, including morphology, adhesion and aggregation. Results showed that the morphology of chondrosarcoma cells at 6h was dependent on the charges of hydrogels; cells present spindle-shaped and round-shaped morphology on negative charged and neutral hydrogel, respectively, while no cells spreaded on positive charged hydrogel. Chondrosarcoma cells formed aggregates on neutral PDMAAm after further culture. The hydrogels can be synthesized easily and has the characteristics of ease at use with defined components, which holds great potential for developing standard chondrosarcoma models in vitro.

Effects of siltuximab on the interleukin-6/Stat3 signaling pathway in ovarian cancer / 中华妇产科杂志

Objective To study the effects of siltuximab on the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) signaling pathway in ovarian epithelial carcinoma.Methods (1) Expressions of IL-6 in ovarian cancer patient specimens were assessed by immunohistochemistry.(2) Expression of phosphorylation Stat3 (pStat3) protein in siltuximab and IL-6 treated SKOV3 cell lines was determined by western blot, and expression levels of Stat3-induced bcl-XL,MCL-1, survivin, in siltuximab treated SKOV3/TR and CAOV3/TR cells lines were also determined by western blot.(3) Real-time image analysis was used to study the nuclear translocation of pEGFP-Stat3 fusion protein in ovarian cancer cell line SKOV3-pEGFP-Stat3 treated with siltuximab and IL-6.(4)Paclitaxel sensitivity in siltuximab treated SKOV3/TR and CAOV3/TR cell lines were assessed using the methyl thiazolyl tetrazolium (MTT).The 50% inhibiting concentration ( IC50 ) was defined as the paclitaxel concentration required to decrease the A490 value to 50%.Results ( 1 ) There were significantly difference in IL-6 staining density and the positive rate of IL-6 protein stained among the metastatic, and drug-resistant recurrent tumors,and matched primary tumors [69%(18/26)] vs.77% (20/26)vs.23% (6/26), P＜0.05].(2)A clear increase in Stat3 phosphorylation levels was observed in the IL-6-treated SKOV3 cell lines as compared to the SKOV3 cell lines.When the IL-6-treated SKOV3 cells were incubated with siltuximab with a range of concentrations of 0.001,0.01,0.1, 1.0 and 10 μg/ml, there were trends toward reduced pStat3 expression in the treated cell lines.Compared without treatment with siltuximab, the expression of the anti-apoptotic proteins MCL-1, bcl-XL and survivin in SKOV3/TR and CAOV3/TR cell lines were significantly decreased after treated with siltuximab.(3) In resting cells, the majority of pEGFPStat3 was cytoplasmic until the addition of human IL-6, which promptly induced the translocation of fluorescent Stat3 molecules to the nucleus.Exposure of cells to siltuximab with a range of concentrations of 0.001, 0.01,0.1, 1.0 and 10 μg/ml, followed by an incubation in IL-6 significantly reduced pEGFP-Stat3 nucleocytoplasmic translocation.(4) MTT cytotoxicity assay demonstrated that siltuximab increased paclitaxel-induced cell death and partially overcame paclitaxel resistance.Treated with siltuximab ( 1 and 10 μg/ml) ,the paclitaxel IC50 value of siltuximab in SKOV3/TR (0.49, 0.19 μg/ml) and CAOV3/TR (0.0010, 0.0008 μg/ml) cells were significantly lower than those in untreated cells (0.71,0.0021 μg/ml;all P ＜ 0.05).Conclusions These results demonstrated that siltuximab effectively block the IL-6 signaling pathways, which .Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer.