Background & objective: The drug-resistance and metastasis in early stages of human malignant ovarian neoplasm have significant effect on chemotherapy of human ovarian carcinoma. The objective of this study was to explore the impact of arsenic trioxide(As2O3) on proliferation and metastasis of drug-resistant human epithelial ovarian carcinoma cell line 3AO/cDDP, in order to treat human ovarian carcinoma thoroughly.
Methods: The growing inhibiting rates of drug-resistant human ovarian carcinoma cell line 3AO/cDDP by various concentrations of As2O3 in different time course were studied by methyl thiazolyl tetrazolium (MTT) method; Apoptosis percentage, cell cycle phase distribution and expressions of Fas, N-myc, nm23H1 and MTA1 gene were estimated by flow cytometry (FCM); 3AO/cDDP cells apoptosis phenotype was observed by transmissional electron microscopy.
Results: 3AO/cDDP cell growing inhibiting rates by As2O3 were significantly different in dose-dependent and time-dependent manners(P < 0.05); Within a certain concentration range, 3AO/cDDP apoptosis inducing rates by As2O3 were dose- and time-dependent, and the most appropriate concentration was 3.0 mumol/L. Lower concentrations of As2O3 perturbed cell progressing through S/G2 phase, while higher concentrations selectively induced S phase cells apoptosis; As2O3 up-regulated Fas and nm23H1 gene expressions, but down-regulated N-myc and MTA1 gene expressions. Morphological observation indicated that As2O3 inducing 3AO/cDDP death characterized by apoptotic phenotype.
Conclusion: As2O3 could influence the capacity of growth and proliferation of drug-resistant human ovarian carcinoma cell line and its mechanism could be positively and negatively related with Fas, nm23H1 gene and N-Myc, MTA1 gene expressions.