title: Expression of AFP and STAT3 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in AFP-producing gastric cancer cells.
abstract: Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC), represented by the production of AFP, has a more aggressive behavior than common gastric cancer. The underlying mechanisms are not well understood. Arsenic trioxide (As(2)O(3)) is used clinically to treat acute promyelocytic leukemia(APL) and has activity in vitro against several solid tumor cell lines, with induction of apoptosis and inhibition of proliferation the prime effects. Signal transducer and activator of transcription 3 (STAT3) has an important role in tumorigenesis of various primary cancers and cancer cell by upregulating cell-survival and downregulating tumor suppressor proteins. Here, we found decreased expression of AFP and STAT3 after induction of apoptosis by As(2)O(3) in the AFPGC FU97 cells. Also, the level of the STAT3 target oncogene Bcl-2 was decreased with As(2)O(3), and that of the tumor suppressor Bax was increased. Furthermore, STAT3 expression and depth of invasion and lymph node metastasis were associated. Survival of patients with gastric cancer was lower with AFP and STAT3 double overexpression than with overexpression of either alone. Downregulation of AFP and STAT3 expression plays an important role in As(2)O(3)-induced apoptosis of AFPGC cells, which suggests a new mechanism of As(2)O(3)-induced cell apoptosis. As(2)O(3) may be a possible agent for AFPGC treatment.
authors: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors: Yanfei
authors: Y
authors: Jia
authors: Dezhi
authors: D
authors: Liu
authors: Dongjie
authors: D
authors: Xiao
authors: Xiaoli
authors: X
authors: Ma
authors: Shuyi
authors: S
authors: Han
authors: Yan
authors: Y
authors: Zheng
authors: Shanhui
authors: S
authors: Sun
authors: Maoxiu
authors: M
authors: Zhang
authors: Hongmei
authors: H
authors: Gao
authors: Xia
authors: X
authors: Cui
authors: Yunshan
authors: Y
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010087:Oxides / Q000494:pharmacology*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001152:Arsenicals; D017077:Culture Media, Conditioned; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D000509:alpha-Fetoproteins; D051028:bcl-2-Associated X Protein; D000077237:Arsenic Trioxide
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