Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. The transition from chemotherapy-responsive breast cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistanceassociated proteins (MRPs). In this study, it was found that TAM-resistant MCF-7 (TAMR-MCF-7) cells expressed higher levels of MRP2 than control MCF-7 cells. Molecular analyses using MRP2 gene promoters supported the involvement of the pregnane X receptor (PXR) in MRP2 overexpression in TAMR-MCF-7 cells. Although CCAAT/enhancer-binding protein b was overexpressed continuously in TAMR-MCF-7 cells, this might not be responsible for the transcriptional activation of the MRP2 gene. In addition, the basal activities of phosphatidylinositol 3-kinase (PI3-kinase) were higher in the TAMR-MCF-7 cells than in the control cells. The inhibition of PI3-kinase significantly reduced both the PXR activity and MRP2 expression in TAMR-MCF-7 cells. Overall, MRP2 induction plays a role in the additional acquisition of chemotherapy resistance in TAM-resistant breast cancer.

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Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase Pin1 and is a central signaling mechanism in cell proliferation and transformation. Although Pin1 is frequently overexpressed in hepatocellular carcinoma (HCC), the molecular mechanism of Pin1 in HCC has not been completely elucidated. Here, we show that Pin1 interacts with p70S6K in vitro and ex vivo. Overexpression of Pin1 resulted in enhanced p70S6K phosphorylation induced by insulin in SK-HEP-1 cells. In contrast, Pin1(-/-) mouse embryonic fibroblasts (MEFs) exhibited significantly decreased insulin-induced p70S6K phosphorylation compared with Pin1(+/+) MEFs. Furthermore, Pin1 enhanced the insulin-induced extracellular signal-regulated protein kinase (ERK)1/2 phosphorylation through its interaction with p70S6K, whereas the inhibition of p70S6K activity by rapamycin suppressed insulin-induced ERK1/2 phosphorylation in SK-HEP-1 cells. Hence, Pin1 affected activator protein-1 activity through p70S6K-ERK1/2 signaling in SK-HEP-1 cells. Most importantly, Pin1-overexpressing JB6 Cl41 cells enhanced neoplastic cell transformation promoted by insulin much more than green fluorescent protein-overexpressing JB6 Cl41 control cells. These results imply that Pin1 amplifies insulin signaling in hepatocarcinoma cells through its interaction with p70S6K, suggesting that Pin1 plays an important role in insulin-induced tumorigenesis and is a potential therapeutic target in hepatocarcinoma.

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Using the casting method novel mucoadhesive polymer blend film consisting of Carbopol, poloxamer, and hydroxypropylmethylcellulose (HPMC) was prepared and characterized. Triamcinolone acetonide (TAA) was loaded into Carbopol/poloxamer/HPMC polymer blend film. Carbonyl band of Carbopol in Carbopol/poloxamer/HPMC shifted to longer wavenumber than that of Carbopol in Carbopol/poloxamer due to the hydrogen bonding among Carbopol, poloxamer, and HPMC. Tan delta peak assigned to glass transition temperature (Tg) of HPMC shifted to low temperature due to increased flexibility caused by increased poloxamer content in polymer blend films. Swelling ratio of Carbopol/poloxamer/HPMC films was lowest in Carbopoll poloxamer/HPMC at mixing ratio of 35/30/35 (wt/wt/wt). Adhesive force of Carbopol/poloxamer/HPMC films increased with increasing HPMC content in Carbopol/poloxamer/HPMC polymer blend film and increasing hydroxypropyl group content in HPMC due to hydrophobic property of HPMC although bioadhesive force was highest at mixing ratio of 35/30/35 (wt/wt/ wt). Release of TAA from TAA-loaded Carbopol/poloxamer/HPMC polymer blend film in vitro increased with increasing loading content of drug.

Sopungyangjae-Tang (SYT) is a traditional Korean decoction used for the treatment of dermatitis. The aim of this study was to confirm whether or not SYT has a preventive effect on the development of atopic dermatitis in dinitrochlorobenzene-applied Nc/Nga mice. SYT was administered orally to Nc/Nga mice, which led to the remarkable suppression of the development of dermatitis, as determined by a histological examination and the serum IgE levels. Moreover, SYT inhibited the production of thymus- and activation-regulated chemokine (TARC) and its mRNA expression in a keratinocyte cell line, HaCaT, which had been stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Activation of the nuclear factor-κB (NF-κB) or activator protein-1 (AP-1) is one of the key steps in the signaling pathways mediating induction of TARC. In this study, SYT selectively suppressed NF-κB activation, which may be essential for TARC expression in TNF-α/IFN-γ treated keratinocytes. The inhibitory effect of SYT on NF-κB activation and TARC production might be associated with the anti-dermatitic effects of SYT.