title: Inhibitory effects of ethyl pyruvate administration on human gastric             cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in             vivo.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jin-Shui
authors.initials: JS
authors.lastname: Zhu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Wei-Xiong
authors.initials: WX
authors.lastname: Chen
authors.forename: Ni-Wei
authors.initials: NW
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D060787:Neoplasm Grading; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D024243:HMGB1 Protein; D011773:Pyruvates; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C046522:ethyl pyruvate; D051057:Proto-Oncogene Proteins c-akt