[Primary study of arsenic trioxide inhibits abdomino-metastatic tumor formation of human ovarian carcinoma in nude mice and its mechanisms].
OBJECTIVE
Arsenic trioxide (As2O3) has been successfully used to treat the patients with acute promyelocyutic leukemia in clinic, and for the experimental studies of liver cancer, colorectal cancer, gastric cancer, etc. The objective of this study was to explore the inhibitory effect of As2O3 on the abdomino-metastasis of human ovarian carcinoma in nude mice and its mechanisms.


METHODS
Compared with cisplatin(cDDP), the growth inhibiting rates to human ovarian cancer cell line 3AO by treatment with various concentrations of As2O3 for 48 h were determined by methyl thiazolyl tetrazolium(MTT) method. After implanted with 3AO cells 4 x 10(6) into abdominal cavity for 96 h, the nude mice were randomly divided into 5 groups and treated by intraperitoneal injection of normal saline, cisplatin, or different concentrations of As2O3. The rate of tumor formation, death rate, and survival period of tumor-bearing nude mice were evaluated. After treatment with As2O3, the changes of Fas, FasL, and nm23 gene expressions were estimated by flow cytometry (FCM).


RESULTS
Compared with cisplatin, 3AO cell growth inhibiting rates by As2O3 were different significantly in concentration-dependent manner (P < 0.05); Compared with cisplatin, As2O3 could reduce the 3AO cell tumor formation rate in nude mice and the death rate of tumor-bearing nude mice, and prolong the survival period of tumor-bearing nude mice significantly (P < 0.05). As2O3 up-regulated Fas and nm23 gene expressions of abdominal cavity implanted tumors (P < 0.05), but did not affect FasL gene expression (P > 0.05).


CONCLUSIONS
As2O3 could inhibit the abdomino-plantation of human ovarian carcinoma in nude mice and its mechanism may be associated with Fas gene and nm23 gene over-expressions.
Huang
Shou-guo
SG
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, P. R. China. shouguohuang@21cn.com
Kong
Bei-hua
BH
Yang
Rui-fang
RF
Jiang
Sen
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D009701:Nucleoside-Diphosphate Kinase; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D010087:Oxides / Q000627:therapeutic use*; D014157:Transcription Factors / Q000096:biosynthesis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D019014:fas Receptor / Q000096:biosynthesis
D000970:Antineoplastic Agents; D001152:Arsenicals; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D054778:NM23 Nucleoside Diphosphate Kinases; D010087:Oxides; D014157:Transcription Factors; D019014:fas Receptor; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins; D000077237:Arsenic Trioxide