Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
PLoS One. 2013;8(1):e54774. doi: 10.1371/journal.pone.0054774. Epub 2013 Jan 30.
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.
甲胎蛋白（AFP）产生的胃癌（AFPGC），以 AFP 的产生为代表，其行为比普通胃癌更具侵袭性。其潜在机制尚未得到很好的理解。三氧化二砷（As2O3）临床上用于治疗急性早幼粒细胞白血病（APL），并在体外对几种实体肿瘤细胞系具有活性，其主要作用是诱导细胞凋亡和抑制增殖。信号转导和转录激活因子 3（STAT3）在各种原发性癌症和癌细胞的肿瘤发生中起着重要作用，通过上调细胞存活和下调肿瘤抑制蛋白。在这里，我们发现 AFPGC FU97 细胞经 As2O3 诱导凋亡后 AFP 和 STAT3 的表达降低。此外，随着 As2O3 的作用，STAT3 靶基因 Bcl-2 的水平降低，而肿瘤抑制因子 Bax 的水平升高。此外，STAT3 表达水平与浸润深度和淋巴结转移有关。与 AFP 和 STAT3 双重过表达的胃癌患者的生存率低于单独过表达的胃癌患者。下调 AFP 和 STAT3 的表达在 As2O3 诱导 AFPGC 细胞凋亡中起着重要作用，提示了 As2O3 诱导细胞凋亡的新机制。As2O3 可能是治疗 AFPGC 的一种潜在药物。
