ABSTRACT
BACKGROUND AND OBJECTIVE: Gemcitabine (GEM) effectively inhibits bladder cancer progression in the clinic, but novel combination treatments using multiple drugs are needed. MATERIALS AND METHODS: The bladder cancer cell lines EJ and UMUC3 were treated with triptolide (TPL) and/or GEM. Tumour cell viability and proliferation were measured using MTT and clonogenic assays, respectively. Flow cytometry and western blotting were used to detect the cell cycle phase, apoptosis, reactive oxygen species (ROS) and the levels of specific relevant proteins. The AKT/GSK3ß signalling pathway proteins were also measured by immunofluorescence and western blotting. RESULTS: The cytotoxicity of the GEM plus TPL combination treatment was stronger than that of GEM or TPL alone. In bladder cancer cell lines, GEM plus TPL induced cell cycle arrest at the G1 phase via suppression of CDK4, CDK6 and cyclins A1 and A2. Significantly increased apoptosis and increases in apoptosis-related proteins (caspase 8 and Bcl-xL) were observed in cells treated with GEM plus TPL. While ROS increased, certain ROS-related proteins (catalase and SOD2) clearly decreased in cells treated with a combination of GEM plus TPL. The AKT/GSK3ß signalling pathway was also inhibited more significantly in cells treated with the GEM plus TPL combination than in cells treated with either agent alone. CONCLUSION: The combination of GEM plus TPL showed significantly enhanced anticancer effects compared to those of GEM or TPL alone.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Deoxycytidine/analogs & derivatives , Diterpenes/pharmacology , Phenanthrenes/pharmacology , Urinary Bladder Neoplasms/drug therapy , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Synergism , Epoxy Compounds/pharmacology , G1 Phase Cell Cycle Checkpoints/drug effects , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , GemcitabineABSTRACT
This study investigated the effect of transcutaneous electrical nerve stimulation (TENS) for the treatment of patients with chronic pain after ankylosing spondylitis (AS).A total of 72 eligible patients with chronic pain following AS were included. All included patients received exercise and were assigned to a treatment group and a control group equally. In addition, patients in the treatment group also underwent TENS therapy. All patients were treated for a total of 6 weeks. The primary outcome of pain intensity was measured by visual analog scale (VAS). The secondary outcomes included degree of functional limitation, as assessed by Bath Ankylosing Spondylitis Functional Index (BASFI); and quality of life, as evaluated by Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. All outcomes were assessed before and after 6 weeks treatment. Furthermore, adverse events were also recorded.After 6-week treatment, patients in the treatment group did not show more promising outcomes in pain reduction, as measured by VAS (Pâ=â.08); functional evaluation, as evaluated by BASFI (Pâ=â.19); as well as quality of life, as assessed by ASQoL (Pâ=â.18), compared with patients in the control group. No adverse events occurred in both groups.This study did not exert encouraging outcomes in patients with chronic pain following AS after 6-week treatment.
