Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking activation of TLR4/MyD88-dependent pathway.

Paclitaxel, a known TLR4 ligand, leads to activation of TLR4/MyD88-dependent pathway that mediates chemoresistance and tumor progression in epithelial ovarian carcinoma (EOC). Atractylenolide-I (AO-I), a novel TLR4-antagonizing agent, inhibits TLR4 signaling by interfering with the binding of LPS or paclitaxel to membrane TLR4 of human leukocytes. In this study, AO-I was found to attenuate paclitaxel-induced protein expression of IL-6, VEGF and survivin, and to enhance early apoptosis and growth inhibition in MyD88(+) EOC cells; AO-I was shown to fit into the hydrophobic pocket of human MD-2 and to partially overlap with the binding site of paclitaxel by docking simulations, suggesting that AO-I may block the MD-2-mediated TLR4/MyD88-dependent paclitaxel signaling in MyD88(+) EOC cells.

Prognostic significance of MyD88 expression by human epithelial ovarian carcinoma cells.

Background: MyD88 is an adaptor protein for TLR-4 signaling known to mediate paclitaxel resistance in epithelial ovarian carcinoma (EOC). This study examined the clinical significance of MyD88 expression in EOC.

Methods: MyD88 and TLR-4 expression were examined by immunocytochemistry in 109 specimens of ovarian tissues, comprising EOC (N = 83), borderline tumors (N = 9), benign cysts (N = 9) and normal ovarian tissue (N = 8), and clinical data collected by a retrospective chart review.

[Influence of human epithelial ovarian cancer HO-8910 cells with modified survivin gene on the cell cycle distribution and chemosensitivity].

Objective: To study the influence of survivin mutant-T34A (survivin(T34A)) and survivin deletant-N-terminal 8 amino acids residues (survivin(N-8AA)) on the cell cycle distribution and chemosensitivity in human ovarian cancer HO-8910 cells for explorating the roles of modified survivin-mediated apoptosis induced by chemotherapeutic agents and possible signaling pathways involved.

Methods: pcDNA3.1 plasmid contained wild-type, survivin(T34A) and survivin(N-8AA) genes were transfected into HO-8910 cells, respectively, the control groups were HO-8910 cells transfected with pcDNA3.

Regulation of hypoxia-induced mRNA expressions of HIF-1alpha and osteopontin and in vitro radiosensitization by tirapazamine in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells.

Background And Objective: Combined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and Tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxia-induced mRNA expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and osteopontin (OPN) in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro.

[In vivo study on influence of a discrete nano-hydroxyapatite on leukemia P388 tissue in BALB/C mice].

Objective: To study the influence of a discrete nano-hydroxyapatite crystal (nano-HAp) on lymphatic leukemia P388 behavior by in vivo techniques.

Methods: A nano-HAp was prepared by a neutralization reaction of 0.1 mol calcium hydroxide suspension and 0.