ABSTRACT
AIM: The aim of the study is to investigate the underlying molecular mechanisms by which gemcitabine (gem) inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells in vitro. MATERIALS AND METHODS: After PANC-1 cells had been treated by indicated concentration (0, 5, and 25 mg/L) of gem for 48 h, cell proliferation was evaluated by 3'-(4, 5 dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay; cell morphology was observed by transmission electron microscopy; Expression of c-IAP2 and Bcl-2 proteins was analyzed by Western blot; the activity of caspase-3 and -9 was detected by spectrophotometry. RESULTS: Gem significantly inhibited cell proliferation and could induce apoptosis of human pancreatic cancer PANC-1 cells, with a dose-dependent manner. Western blot analysis showed that gem significantly reduced c-IAP2 and Bcl-2 proteins expression level (P < 0.05). Spectrophotometric assay showed that gem significantly increased caspase-3 and -9 activity in PANC-1 cells. CONCLUSION: Gem could induce apoptosis of human pancreatic cancer PANC-1 cells, probably through downregulating c-IAP2 and Bcl-2 expression levels, and at the same time activating caspase-3 and -9.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Deoxycytidine/analogs & derivatives , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/pharmacology , Enzyme Activation/drug effects , Gene Expression Regulation/drug effects , Humans , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/ultrastructure , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , GemcitabineABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical features and outcome of patients with noncompaction of ventricular myocardium (NVM).</p><p><b>METHODS</b>Clinical manifestations, electrocardiograms and echocardiographies data were analyzed in 18 patients with NVM. Mean follow-up period was (11 +/- 5) months.</p><p><b>RESULTS</b>The patients aged from 1.5 to 71 years, 66.7% patients were males, familial history was observed in 2 cases, congestive heart failure was present in 14 cases, thromboembolic event occurred in 1 patient, arrhythmia induced syncopes were diagnosed in 2 patients and 1 patient was asymptomatic. Abnormal electrocardiograms were observed in all patients, including premature ventricular beats (7 cases), heart block (4 cases), and atrial fibrillations (4 cases). Echocardiographies showed that noncompaction of ventricular myocardium localized in the left ventricle in 17 patients, and right ventricle in 1 patient. The extension of noncompaction myocardium was predominantly at the apex (72%). N/C was 2.3 - 3.1. EF was less than 50% in 15 patients. Hypokinetic movements were observed in both noncompacted and compacted segments. During the follow-up, 1 patient with congestive heart failure received heart transplantation. ICD was implanted in one patient due to ventricular tachycardia. One patient suffered from sudden cardiac death.</p><p><b>CONCLUSIONS</b>The most common clinical presentations of NVM are congestive heart failure, cardiac arrhythmias, and thromboembolism. Echocardiography is considered as the best tool for the diagnosis of NVM. ICD, heart transplantation and anticoagulation therapy could improve the prognosis of patients with NVM in selected cases.</p>
