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Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: Therapeutic potential for ovarian cancer
Cancer Science, 09/30/09

Zhang N et al. – ATO and its combination with CDDP present therapeutic potential for ovarian cancer, and deserve further preclinical and clinical studies.

Methods

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 down-regulated genes) may strongly associate with the antiproliferative and pro-apoptotic effects induced by ATO
Chou–Talalay 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

Results

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 IC50 to IC90 in suspension COC1 cells where CI < 1, =1, and >1, define synergism, additive effect, and antagonism, respectively
the combination of ATO and CDDP yielded favorable DRIs ranging from 1.23-fold to 13.51-fold dose reduction

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