071%) and liposome negative control group (2.759%) [tumor inhibition = (mean tumor weight of control group - mean tumor weight of treatment group)/(mean tumor weight of control group) �� 100%]. Telomerase activity was significantly lower (P < 0.01) in the PS-ASODN group (0.689 �� 0.158) compared with the imatinib group (1.838 �� 0.241), liposome negative control group http://www.selleckchem.com/products/lapatinib.html (2.013 �� 0.273), and saline group (2.004 �� 0.163). Flow cytometry revealed that the apoptosis rate of tumor cells treated with PS-ASODN was 20.751% �� 0.789%, which was higher (P < 0.01) than that of the imatinib group (1.163% �� 0.469%), liposome negative control group (1.212% �� 0.310%), and saline group (1.172% �� 0.403%). Expression of bcl-2 mRNA in the transplanted GISTs was markedly downregulated (P < 0.01) in the PS-ASODN group (7.
245 �� 0.739) compared with the imatinib group (14.153 �� 1.618) and liposome negative control group (16.396 �� 1.351). CONCLUSION: PS-ASODN can repress GIST growth, mediated perhaps by inhibition of telomerase activity and downregulation of bcl-2 expression. Keywords: Gastrointestinal stromal tumor, Phosphorothioate antisense oligonucleotides, Imatinib, Tumor inhibitory rate, Telomerase activity Core tip: Gastrointestinal stromal tumors (GISTs) are low-grade malignant mesenchymal tumors of the gastrointestinal tract. In our study, telomerase activity was repressed and the level of B-cell leukemia/lymphoma 2 mRNA markedly downregulated in SCID mice carrying transplanted human GISTs and treated with telomerase RNA-targeting phosphorothioate antisense oligodeoxynucleotides (PS-ASODN).
Therefore, the therapeutic effect of PS-ASODN on GISTs is remarkable. INTRODUCTION Gastrointestinal stromal tumor (GIST) is a recently recognized tumor entity. It is now evident that GIST is a distinct tumor type and the most common sarcoma of the gastrointestinal tract in humans[1]. GISTs account for 2.2% of morbidity associated with malignant tumors of the gastrointestinal tract[2]. GISTs occur at a median age of 60 years, with a slight male predominance. Approximately 60% and 30% of GISTs arise in the stomach and small intestine, respectively. GISTs have a high propensity for metastatic relapse, specifically in the liver and peritoneum, after initial surgery for localized disease[3,4].
GISTs are currently categorized based on cell morphology, namely spindle cell, GSK-3 epithelioid, or occasionally pleomorphic; the tumors generally arise in the gastrointestinal tract and usually express the protein KIT. GISTs are generally resistant to conventional cancer chemotherapy and are associated with poor outcome; in 2001, however, an adjuvant therapy with the tyrosine kinase inhibitor imatinib was found to be highly effective against GIST[5]. Although imatinib has revolutionized the treatment of advanced GISTs, clinical resistance to this drug has proved to be a substantial problem requiring prolonged treatment[6,7].