Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, PR China.
Oncol Rep. 2012 May;27(5):1511-9. doi: 10.3892/or.2012.1623. Epub 2012 Jan 9.
The high mobility group box-B1 (HMGB1)-receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. Ethyl pyruvate (EP), a potent inhibitor of HMGB1 release, can exert antitumor effects on the growth of gastric cancer. Therefore, it is necessary to observe the effects of EP on gastric cancer growth in vitro and in vivo. Human gastric adenocarcinoma tissues of different grades (N=45) were collected. The expression of HMGB1 and RAGE was evaluated immunohistochemically in biopsy samples. After SGC-7901 gastric cancer cells were treated with EP, the expression of HMGB1, RAGE, Akt, phosphorylated Akt (p-Akt) and some transcription factors was identified and the effects of EP on cell proliferation, invasion, cell cycle distribution and apoptosis were assessed. A subcutaneous xenograft tumor model was established, validating the effects of EP on tumor growth in vivo. The expression of HMGB1 and RAGE was respectively observed in 73.3 and 68.9% of the gastric adenocarcinoma tissues. The frequency of positive expression increased with the ascending grade of the tumor malignancy. EP decreased the expression of HMGB1, RAGE, Akt, p-Akt, Ki-67 and matrix metallopeptidase-9 (MMP‑9), and increased the expression of p53. Moreover, EP could inhibit tumor cell proliferation and invasion, induce cell cycle arrest and apoptosis and slow the growth of xenograft tumors. In conclusion, HMGB1 and RAGE were strongly expressed in gastric adenocarcinoma, and EP administration inhibited gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways. EP may play a critical role in the treatment of cancer in conjunction with other therapeutic agents.
高迁移率族蛋白 B1（HMGB1）-晚期糖基化终产物受体（RAGE）和蛋白激酶 B（Akt）途径在许多恶性肿瘤的发生和发展中起着至关重要的作用。丙酮酸乙酯（EP）是一种有效的 HMGB1 释放抑制剂，可对胃癌的生长发挥抗肿瘤作用。因此，有必要观察 EP 对胃癌生长的体内外作用。收集了不同分级的人胃腺癌组织（N=45）。采用免疫组化法检测活检样本中 HMGB1 和 RAGE 的表达。用 EP 处理 SGC-7901 胃癌细胞后，鉴定 HMGB1、RAGE、Akt、磷酸化 Akt（p-Akt）和一些转录因子的表达，并评估 EP 对细胞增殖、侵袭、细胞周期分布和凋亡的影响。建立皮下异种移植肿瘤模型，验证 EP 对体内肿瘤生长的影响。HMGB1 和 RAGE 的表达分别在 73.3%和 68.9%的胃腺癌组织中观察到。阳性表达的频率随着肿瘤恶性程度的升高而增加。EP 降低了 HMGB1、RAGE、Akt、p-Akt、Ki-67 和基质金属蛋白酶-9（MMP-9）的表达，增加了 p53 的表达。此外，EP 可抑制肿瘤细胞增殖和侵袭，诱导细胞周期停滞和凋亡，减缓异种移植肿瘤的生长。总之，HMGB1 和 RAGE 在胃腺癌中强烈表达，EP 通过调节 HMGB1-RAGE 和 Akt 途径抑制胃癌生长。EP 可能与其他治疗药物一起在癌症治疗中发挥重要作用。
