title: Inhibition of activated Stat3 reverses drug resistance to chemotherapeutic agents in gastric cancer cells.
abstract: Multidrug resistance is a major obstacle in the treatment of gastric cancer. The underlying mechanisms of this phenomenon have not been well understood. Accumulating evidence indicates that Stat3 plays an important role in tumorigenesis of various primary cancers and cancer cell lines by upregulating cell survival proteins and downregulating tumor suppressors. We propose that the Stat3 pathway is also involved in acquired drug resistance of gastric cancer. To test this hypothesis, we investigated the expression and activation of Stat3 in drug resistant gastric cancer cell lines. Western blotting and real-time reverse transcription-PCR determined that Stat3 and its target genes were overactivated and/or overexpressed in drug resistant cells. Inhibition of Stat3 function resulted in significant decreases in cisplatin resistance and enhanced apoptosis in drug resistant cells. The levels of Stat3 target oncogenes such as Bcl-2 and c-Myc were decreased with DPP, a Stat3 inhibitor, treatment, while the expression of tumor suppressor p53 was increased. Interestingly, the vacuolar ATPase, a proton pump which interferes the uptake of therapeutic drugs, was down regulated by Stat3 inhibition. In conclusion, these data supported the hypothesis that interruption of Stat3 signaling could reverse resistance to chemotherapy agents in human gastric cancer cells.
authors: Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China.
authors: Shuling
authors: S
authors: Huang
authors: Min
authors: M
authors: Chen
authors: Yonghua
authors: Y
authors: Shen
authors: Weidong
authors: W
authors: Shen
authors: Huimin
authors: H
authors: Guo
authors: Qian
authors: Q
authors: Gao
authors: Xiaoping
authors: X
authors: Zou
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D016133:Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; D002945:Cisplatin