title: Evodiamine sensitizes BGC-823 gastric cancer cells to radiotherapy in vitro and in vivo.
abstract: The present study aimed to investigate the ability of evodiamin (EVO) to sensitize BGC-823 gastric cancer cells to radiotherapy and to elucidate the underlying mechanisms. First, the sensitizing effects of EVO to radiation were demonstrated in vitro using an MTT and a clonogenic assay. Flow cytometric analysis further revealed that the inhibition of cell cycle progression of BGC-823 cells by radiation was enhanced by EVO in vitro. Furthermore, BGC-823 cell-derived xenograft models were established and animals were divided into the following four treatment groups: Control group, evodiamin group, radiotherapy group and combined therapy group. The volume and weight of the xenograft tumors were measured, from which the tumor the tumor growth curve was drawn and the inhibition rate was calculated, respectively. The results revealed that combined therapy inhibited tumor growth to a greater extent than mono treatments. The tumor inhibition rate and the level of apoptosis in the combination group (48.8%) were significantly higher than those in the other groups (P<0.05). Immunohistochemistry was used to reveal that the expression of Bcl‑2, phosphorylated Akt and Her‑2 was significantly decreased, while Bax was increased in the xenograft tumors subjected to radiation, which was significantly enhanced by EVO. In conclusion, EVO was demonstrated to sensitize BGC-823 cells to radiation therapy and markedly inhibited xenograft tumor growth. Furthermore, downregulation of Her‑2/AKT/Bcl-2 signaling was shown to be involved in this process. These results suggested that EVO may be a good candidate for combined therapy with radiation in the treatment of human gastric cancer.
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Chengqi
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Xuexiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Urology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oral Medicine, School of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D051028:bcl-2-Associated X Protein; C049639:evodiamine