Bladder cancer (BCa) threatens human health due to the high occurrence and mortality. Nowadays, more and more researchers focussed on the molecular mechanisms and biological functions of miRNAs in human cancers. The present study aims to study the biological role of miR-454-3p and miR-374b-5p in BCa. The expression levels of miR-454-3p and miR-374b-5p were detected in BCa tissues and cell lines by qRT-PCR analysis. Kaplan–Meier analysis revealed that the expression levels of miR-454-3p and miR-374b-5p were positively correlated with the overall survival (OS) rate of BCa patients. Gain-of-function assays were conducted to demonstrate the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion, migration, and epithelial–mesenchymal transition (EMT) of BCa cells. Mechanically, ZEB2 was found to be a target of both miR-454-3p and miR-374b-5p. Rescue assays revealed that ZEB2 reversed the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion and migration of BCa cell lines. In summary, miR-454-3p and miR-374b-5p negatively regulated invasion and migration of BCa cell lines via targetting ZEB2.
Nobiletin is a polymethoxy flavonoid isolated from Citrus depressa and Citrus reticulata. It has been reported that nobiletin can suppress tumors. We primarily explored the antitumor effects of nobiletin and the associated potential mechanisms in ACHN and Caki-2 renal carcinoma cells. A CCK-8 assay and cloning experiments were used to assess cell viability, and a transwell assay and scratch test were used to assess metastatic ability. The cell cycle was analyzed by flow cytometry, whereas apoptosis was analyzed using flow cytometry and a terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. Protein expression was examined by Western blot and immunofluorescence. Renal cancer cells were subcutaneously transplanted into nude mice for in vivo studies. The data showed that nobiletin administration significantly dose-and time-dependently suppressed renal cancer cell proliferation; moreover, nobiletin treatment induced cell cycle arrest in the G0/G1 phase and promoted apoptosis. Immunofluorescence analysis indicated that nobiletin decreased the nuclear localization of signal transducer and activator of transcription 3 (STAT3) and YY1-associated protein 1 (YY1AP1). Western blot showed that the levels of phosphorylated SRC, phosphorylated AKT serine/threonine kinase (AKT), and phosphorylated STAT3 were decreased, whereas that of phosphorylated YY1AP1 was increased. The results further showed that application of insulin-like growth factor 1 (IGF1) was able to reverse the nobiletin-induced changes in the levels of phosphorylated AKT, phosphorylated STAT3, and phosphorylated YY1AP1, and could also reverse the antitumor effects of nobiletin. The results of in vivo experiments showed that, compared to the control, tumor volume and weight were both reduced following nobiletin treatment. In conclusion, our study demonstrated that nobiletin can inhibit renal carcinoma cell viability and provides a novel therapeutic approach for the treatment of kidney cancer.
Near-infrared fluorescence (NIRF) imaging is a novel imaging modality that allows for detection and real‑time monitoring of various pathophysiological states. IR-780 iodide has been used as an ideal platform to construct theranostic agents for cancer imaging and therapy. Abiraterone is a 17α‑hydroxylase/C17, 20‑lyase (CYP17) inhibitor that has been approved for use in patients with prostate cancer after androgen deprivation therapy. We report the synthesis and characterization of IR-780 conjugated abiraterone for the dual purpose of prostate cancer imaging and therapy. The new compound Abi-780 retained the excellent photophysical characteristics and NIRF imaging property of IR-780 dye. Abi-780 preferentially accumulated in plasmonic organelles of prostate cancer cells but not in normal prostate epithelial cells. Dose-dependent inhibition of cultured prostate cancer cells by Abi-780 was found. Abi-780 at 20 µM significantly reduced the capabilities of colony formation and migration/invasion potential as well as increasing the apoptosis rate of prostate cancer cells. NIRF imaging using Abi-780 selectively identified the tumors in mice bearing prostate cancer xenografts. Moreover, Abi-780 treatment significantly retarded the tumor growth. No severe systemic toxicity was observed in mice with daily injection of high-dose Abi-780 for one month. In conclusion, biocompatible Abi-780 is highly effective both in prostate cancer imaging and therapy. Constructing theranostic agents using the NIRF dye platform holds great promise in accurate diagnosis and targeted treatment of cancer.
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