Then, the expression levels of the Wnt/beta-catenin signaling pathway-related proteins beta-catenin and Wnt inhibitory factor-1 (WIF-1) were measured to investigate their possible roles in the antitumor effect of fulvestrant. The cells were also treated with decitabine (10 mu M) to investigate the epigenetic ON-01910 Cell Cycle inhibitor mechanism of WIF-1 expression. The proliferation of MMQ cells and the secretion of PRL were suppressed by fulvestrant in a dose-dependent manner (up to 57.0 +/- 3.9 % and 51.2 +/- 4.9 %, respectively). beta-Catenin
expression was downregulated and was positively correlated with ER-alpha expression (P smaller than 0.01). As a tumor suppressor, WIF-1 expression was upregulated and was negatively correlated Ilomastat clinical trial with ER-alpha expression (P smaller than 0.01). Furthermore, WIF-1 expression was upregulated via the hypomethylation of the promoter by decitabine, and cellular proliferation was correspondingly suppressed (37.8 +/- 4.3 %). Antitumor effect of fulvestrant was partially disrupted by SB 216763 via activation of the Wnt/beta-catenin pathway. In conclusion, through the Wnt/beta-catenin signaling pathway,
fulvestrant can suppress the proliferation of MMQ cells and the secretion of PRL.”
“Background: There is large variability among lung squamous cell carcinoma patients in response to treatment with cisplatin based chemotherapy. LncRNA is potentially a new type of predictive marker that can identify subgroups of patients who benefit from chemotherapy and it will have great value for treatment guidance. Methods: Differentially expressed lncRNAs and mRNA were identified using microarray profiling of tumors with partial response (PR) vs. with progressive disease (PD) from advanced lung squamous cell carcinoma patients
treated with cisplatin based chemotherapy and validated by quantitative real-time PCR (qPCR). Furthermore, the expression of AC006050.3-003 was assessed in another 60 tumor samples. Results: Compared with the PD samples, 953 lncRNAs were consistently upregulated and selleck chemicals llc 749 lncRNAs were downregulated consistently among the differentially expressed lncRNAs in PR samples (Fold Change bigger than = 2.0-fold, p smaller than 0.05). Pathway analyses showed that some classical pathways, including “Nucleotide excision repair,” that participated in cisplatin chemo response were differentially expressed between PR and PD samples. Coding-non-coding gene co-expression network identified many lncRNAs, such as lncRNA AC006050.3-003, that potentially played a key role in chemo response. The expression of lncRNA AC006050.3-003 was significantly lower in PR samples compared to the PD samples in another 60 lung squamous cell carcinoma patients. Receiver operating characteristic curve analysis revealed that lncRNA AC006050.3-003 was a valuable biomarker for differentiating PR patients from PD patients with an area under the curve of 0.887 (95% confidence interval 0.779, 0.954).