Open AccessArsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: Therapeutic potential for ovarian cancer
Author(s) -
Zhang Ning,
Wu ZhenMing,
McGowan Eileen,
Shi Jun,
Hong ZuBei,
Ding ChuanWei,
Xia Pu,
Di Wen
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01340.x
Subject(s) - ovarian cancer , arsenic trioxide , cisplatin , mtt assay , cytotoxicity , apoptosis , pharmacology , annexin , cancer research , growth inhibition , cancer cell , chemistry , cancer , biology , medicine , in vitro , chemotherapy , biochemistry
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 down‐regulated genes) may strongly associate with the antiproliferative and pro‐apoptotic effects induced by ATO. Furthermore, 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. 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)