Antitumor effect and mechanisms of arsenic trioxide on subcutaneously implanted human gastric cancer in nude mice.
We sought to investigate the efficacy of arsenic trioxide (As(2)O(3)) against a human gastric cell line implanted in nude mice in vivo, as well as the mechanism involved. The solid tumor model was created in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into animals in two arsenic-treated groups (2.5 mg/kg and 5 mg/kg), and the same volume of saline solution was injected into the control group. The inhibitory effect was observed in every group. Apoptotic cells and apoptotic bodies were observed by transmission electron microscope; the fraction of apoptotic cells was detected by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) under laser confocal technology. The expression of Fas and FasL was detected by immunohistochemical staining. In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3), approximately 50% and 30% tumor growth inhibition were observed, respectively (P < 0.05 for both treatment groups). Increase in apoptotic cells and apoptotic bodies appeared in As(2)O(3)-treated tumors compared with the control group. The fluorescence intensity levels of apoptotic cells in tumor were significantly higher in the arsenic-treated groups (P < 0.05 for both treatment groups). The fluorescence intensity level of apoptotic cells in the 5-mg/kg group was higher than that in the 2.5-mg/kg group (P < 0.05). The expression of Fas protein increased in dose- and time-dependent manner after the treatment with As(2)O(3), but that of FasL protein showed no significant difference between control and treated groups. As(2)O(3) did not induce hepatic and renal system injury in the nude mice. As(2)O(3) can inhibit the growth of human gastric cell implanted tumor. We ascribe this to upregulation of Fas, which can induce apoptosis of gastric cells.
Wu
De-Dong
DD
Baoji Municipal Central Hospital, Baoji, Shaanxi Province, 0086-721008, China. wudedong0718@yahoo.cn
Xiao
Yan-Feng
YF
Geng
Yi
Y
Hou
Jie
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D040521:Subcutaneous Tissue; D016042:Transplantation, Heterotopic; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide