Expression of AFP and STAT3 Is Involved in Arsenic Trioxide-Induced Apoptosis and Inhibition of Proliferation in AFP-Producing Gastric Cancer Cells

by Yanfei Jia, Dezhi Liu, Dongjie Xiao, Xiaoli Ma, Shuyi Han, Yan Zheng, Shanhui Sun, Maoxiu Zhang, Hongmei Gao, Xia Cui, Yunshan Wang

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 (As₂O₃) 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 As₂O₃ in the AFPGC FU97 cells. Also, the level of the STAT3 target oncogene Bcl-2 was decreased with As₂O₃, 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 As₂O₃-induced apoptosis of AFPGC cells, which suggests a new mechanism of As₂O₃-induced cell apoptosis. As₂O₃ may be a possible agent for AFPGC treatment.

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Expression of AFP and STAT3 Is Involved in Arsenic Trioxide-Induced Apoptosis and Inhibition of Proliferation in AFP-Producing Gastric Cancer Cells
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Source: http://elitestv.com/pub/2013/01/expression-of-afp-and-stat3-is-involved-in-arsenic-trioxide-induced-apoptosis-and-inhibition-of-proliferation-in-afp-producing-gastric-cancer-cells

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