ABSTRACT
OBJECTIVES: Baicalein is a Chinese traditional medicine that inhibits tumor migration and growth. Pancreatic neuroendocrine tumors (pNETs) have a high incidence in China, but there are still no effective treatments. The aim of our study was to investigate whether baicalein could inhibit pNETs. METHODS: In vitro, we used BON1-a cell line of pNETs-to analyze the apoptosis and migration and invasion after baicalein treatment via flow cytometry and Western blot. In vivo, we used a xenograft tumors model to evaluate the size of tumors after baicalein treatment. Western blot was used to analyze the expression of apoptosis and migration-related protein. RESULTS: In vitro, the Cell Counting Kit 8 assay showed that baicalein decreased BON1 viability, and flow cytometry demonstrated that baicalein induced BON1 apoptosis and protein changes. In addition, baicalein inhibited BON1 migration and invasion as shown via a Transwell assay. In vivo, baicalein inhibited tumor growth and migration and also increased apoptosis-related protein expression. CONCLUSIONS: Baicalein could increase caspase-3 and Bax expression and decrease survivin and Bcl-2 to induce apoptosis. It inhibits migration and invasion by decreasing expression of vascular endothelial growth factor and matrix metalloproteinases 2 and 9.
Subject(s)
Cell Movement/drug effects , Flavanones/pharmacology , Neuroendocrine Tumors/drug therapy , Pancreatic Neoplasms/drug therapy , Xenograft Model Antitumor Assays , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Caspase 3/metabolism , Cell Line, Tumor , Female , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Nude , Neoplasm Invasiveness , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathologyABSTRACT
BACKGROUND & AIMS: Pinaverium bromide (pinaverium) is an antispasmodic commonly used to treat irritable bowel syndrome (IBS), but there has been no convincing evidence for its effectiveness and safety. We evaluated these in a prospective, double-blind, placebo-controlled trial. METHODS: Patients with IBS, based on Rome III criteria, were assigned randomly to groups given pinaverium (50 mg, 3 times/day; n = 218) or placebo (3 times/day; n = 209) at 4 hospitals in China, from August 2012 through December 2013. The primary end points were reductions in abdominal pain and Bristol stool score. Secondary end points were reductions in pain and stool frequencies and abdominal discomfort and its frequency. We also evaluated changes in IBS global symptom scores and the number of adverse effects. RESULTS: Based on an intention-to-treat analysis, a significantly larger proportion of patients receiving pinaverium met either of the primary end points (50.0% met an end point at week 2, and 77.5% met an end point at week 4), compared with placebo (P < .001). Pinaverium reduced at least 1 secondary end point in significantly more patients receiving pinaverium (76.1% had a reduction at week 2, and 91.7% had a reduction at week 4) than placebo (P < .001). Based on symptom scores, significantly higher percentages of patients receiving pinaverium believed that their IBS symptoms improved (60%) than in the placebo group (34%; P < .001); 29% of patients in the pinaverium group believed that their IBS symptoms stayed the same (29%) and 11% said they worsened. Pinaverium was not associated with severe adverse effects; common side effects included nausea (3.7%), dizziness (3.2%), increased blood pressure (2.3%), and abdominal discomfort (2.3%). CONCLUSIONS: Based on a controlled trial, pinaverium reduces symptoms of IBS. It can be considered a first-line treatment for IBS. TRIAL REGISTRATION: NCT01641224 (www.ClinicalTrials.gov).
