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Drug resistance is a major concern in the successful treatment of ovarian cancer. In the present study we report a combinational drug regime using arsenic trioxide (ATO) and cisplatin (CDDP) to increase therapeutic potentiality in ovarian cancer cells. ATO-mediated growth inhibition and apoptosis in human suspension ovarian cancer COC1 cells were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. cDNA arrays were performed to screen ATO-mediated gene expression. Treatment of COC1 cells with ATO alone resulted in growth inhibition and apoptosis with a dose-and time-dependent fashion; further cDNA arrays showed that 34 genes (23 up-regulated genes and 11 downregulated genes) may strongly associate with the antiproliferative and pro-apoptotic effects induced by ATO. Furthermore, ChouTalalay analysis was used to evaluate the combinational effect of ATO and CDDP as well as dose-reduction index (DRI) in a panel of ovarian cancer cells including CDDP-sensitive and -resistant cell lines. The combination index (CI) analysis indicated that the interaction effect of ATO/CDDP exhibited a wide range of synergism in all the adherent ovarian cancer cells (A2780, IGROV-1, SKOV-3, and R182) as well as 0.93 to 0.69 for IC 50 to IC 90 in suspension COC1 cells where CI < 1, =1, and >1, define synergism, additive effect, and antagonism, respectively. More intriguingly, the combination of ATO and CDDP yielded favorable DRIs ranging from 1.23-fold to 13.51-fold dose reduction. These results suggest that ATO and its combination with CDDP present therapeutic potential for ovarian cancer, and deserve further preclinical and clinical studies. (Cancer Sci 2009; 100: 2459-2464 O varian carcinoma still ranks first as the leading cause of death among gynecological malignancies. (1) Platinum compounds are the key components of chemotherapy for the treatment of ovarian cancer patients. However, drug resistance is a significant obstacle hindering the successful treatment of ovarian cancer patients. As documented, patients with ovarian cancer had a 5-year survival rate of less than 30%. (2) Therefore, new therapeutic agents and new regimens consisting of combinations of chemotherapeutic agents are needed.Arsenic trioxide (ATO) is a natural substance that has been used medically as a traditional Chinese medicine for over a thousand years, following the ancient philosophy of ''treating an evil with a toxic''. (3) Approval by the Food and Drug Administration for the use of ATO in the treatment of relapsed/refractory acute promyelocytic leukemia (APL) in the 1990s was supported by the impressive clinical response rates in Chinese patients with APL (4) and confirmative clinical studies conducted in the USA. (3) Remarkable efficacy of ATO in the treatment of APL led to exploration of its anticancer activity and underlying mechanism in other malignancies. There has been promising laboratory and pre-or clinical effects observed in various hematologic malignancies (5,6) and in a variety of solid tumors. (7)(8)(9)(10) We, as we...