STC1 ameliorates cognitive impairment and neuroinflammation of Alzheimer's disease mice via inhibition of ERK1/2 pathway.

OBJECTIVE: To investigate the regulatory role of STC1 (Stanniocalcin-1) mediated ERK1/2 pathway in cognitive impairment and neuroinflammation of Alzheimer's disease (AD). METHODS: WT mice and STC1 Tg mice (transgenic overexpression of STC1) were used to establish AD models to perform behavioral test by Morris water maze. Hippocampal cell apoptosis was quantified by TUNEL staining, the levels of inflammatory cytokines in serum and hippocampal tissues determined by ELISA, as well as oxidative stress-related factors detected by corresponding testing kits, and protein expression of STC1 and ERK1/2 pathway measured by Western blotting. RESULTS: Compared with WT Sham group, WT AD mice had prolonged escape latency, decreased crossing platform times, increased hippocampal cell apoptosis with up-regulated inflammatory cytokines and oxidative stress-related factors, as well as increased STC1 and ERK1/2 pathway-related molecules. By contrast, STC1 Tg AD mice showed shortened escape latency, increased crossing platform times than WT AD mice, and they also exhibited the decreased apoptosis index and inflammatory cytokines, alleviated oxidative stress-injury, down-regulated protein expression of ERK1/2 pathway, and up-regulated the protein expression of STC1 and UCP2. CONCLUSION: STC1 overexpression could alleviate oxidative stress-induced injury, reduce neuroinflammation, improve cognitive function to play a neuro-protective role by inhibiting ERK1/2 signaling pathway.

[Effect of adenovirus-mediated mutant exogenous P27kip1 gene expression on the chemosensitivities of cholangiocarcinoma cell line].

OBJECTIVE: To investigate the effects of mutant exogenous P27(kip1) gene on chemosensitivity of human cholangiocarcinoma cell line. METHODS: The recombinant vector was constructed and the mutant P27(kip1) gene was transfected into human cholangiocarcinoma cell line (QBC(939)). RT-PCR and Western blot were used to determine the expression of target genes. The effects of 5-fluorouracil (5-FU), mitomycin C (MMC) and cyclophosphamide (CTX) on the transfected cells were detected by assaying the apoptotic rate and growth inhibition by methabenzthiazuron (MTT) assay and flow cytometry (FCM). RESULTS: The mutant exogenous P27(kip1) gene was expressed effectively in the cells, and the expression enhanced the apoptosis and growth inhibition of QBC(939) inducted by 5-FU, MMC and CTX. The ratio of growth inhibiting increased significantly from 41.89% (5-FU), 45.59% (MMC), 38.91% (CTX) to 56.15% (5-FU), 55.65% (MMC), 51.69% (CTX), and apoptosis index from 13.76% +/- 3.03% (5-FU), 11.76% +/- 3.99% (MMC), 10.46% +/- 2.10% (CTX) to 41.39% +/- 4.32% (5-FU), 35.94% +/- 2.71% (MMC), 34.46% +/- 2.32% (CTX) (P < 0.05). CONCLUSIONS: The exogenous P27(kip1) gene transfer can remarkably increase the drug sensibility of the cholangiocarcinoma cells. The strategy targeted to control the cell cycle may be more effective in cancer treatment by combination of P27(kip1) gene therapy.