[Apoptosis of drug-resistant human ovarian carcinoma cell line 3AO/cDDP induced by arsenic trioxide and its mechanism].
OBJECTIVE
To explore the effects of arsenic trioxide (As(2)O(3)) on the growth of drug-resistant human epithelial ovarian carcinoma cell line 3AO/cDDP and its possible mechanism.


METHODS
Human epithelial ovarian carcinoma cell line 3AO and drug-  resistant human epithelial ovarian carcinoma cell line 3AO/cDDP were cultured   As(2)O(3) of different concentrations was added into the media. Cell culture without addition of As(2)O(3) was used as control. The growth inhibiting rates of 3AO/cDDP cells with various concentrations of As(2)O(3) in different time course (24, 48, 72, and 96 hours after) were studied by methyl thiazolyl tetrazolium (MTT) method. The apoptosis percentage, cell cycle phase distribution and expression of Fas/FasL gene were estimated by flow cytometry (FCM). The apoptosis phenotype of 3AO/cDDP cells was observed by cytoskeleton dying, and the apoptosis phenotype of 3AO cells was observed by acridine dying under fluorescent microscopy.


RESULTS
3AO/cDDP cell growing inhibiting rates by As(2)O(3) were different significantly in dose-dependent and time-dependent manners (P < 0.05). Within a certain concentration range, 3AO/cDDP apoptosis inducing rates by As(2)O(3) were dose -and time-  dependent, and the most appropriate concentration was 3.0 micromol/L; lower concentrations of As(2)O(3) perturbed the cells to progress through S/G(2) phase, while higher concentrations of As(2)O(3) selectively induced apoptosis of S phase cells. As(2)O(3) up-regulated Fas gene expression, but did not affect FasL gene expression in both cell lines without significant difference (P > 0.05).   Morphological observation indicated that As(2)O(3) induced typical apoptotic bodies in 3AO/cDDP and 3AO cells.


CONCLUSIONS
As(2)O(3) effectively inhibits the proliferation of drug-resistant human ovarian carcinoma cell line through up-regulating Fas gene expression and inducing apoptosis of cells in S phase.
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China.
Shouguo
S
Huang
Beihua
B
Kong
Yuyan
Y
Ma
Sen
S
Jiang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics
D000970:Antineoplastic Agents; D001152:Arsenicals; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D010087:Oxides; D019014:fas Receptor; D000077237:Arsenic Trioxide