Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice

Abstract

BackgroundHepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model.MethodsThe effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells.ResultsIMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS.ConclusionsIMOS is a potential anti-HCC candidate through inhibition of ERK and JNK signaling independent of p53 and worth studying further in patients with HCC, especially at advanced stages.

MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming

“…Details on Western blotting, RNA extraction, real-time PCR [24,26], RNA immunoprecipitation and sequencing [27], luciferase reporter assay [28], miRNA in situ hybridization, patient selection and tissue microarray (TMA) construction [29], immunofluorescence staining, immunohistochemical staining [30], and functional assays, such as migration, and Matrigel invasion assays [19], wound healing assays [31], in vivo assays for tumor metastasis [32,33], cell membrane fluidity evaluated by TMA-DPH, statistical analysis [28], are described in the Additional file 6.…”

MicroRNA-10a Is Involved in the Metastatic Process by Regulating Eph Tyrosine Kinase Receptor A4-Mediated Epithelial-Mesenchymal Transition and Adhesion in Hepatoma Cells

“…MTT was added to each well and incubated for another 4 hours. The number of adherent cells was estimated by reading the absorbance at a wavelength of 570 nm 30…”

The Carbohydrate Prebiotics and Prospects of Their Use

“…Наряду с существующиìи данныìи о способности изоìальтулозы оказывать пребиоти÷еский эффект in vitro [1], появились сообщения об эффективноì ее приìенении как пребиоти÷еской добавки в раöио-не питания людей, страдающих серде÷нососудистыìи заболеванияìи, атеросклерозоì, нарушениеì обìена веществ [5, 57, 68]. Êроìе того, в экспериìентах на животных показано, ÷то употребление изоìальтулозы в сульфатированной форìе оказывает противоопухолевый эффект [65].…”