In Vitro Interaction of Taxol with Other Antitumor Drugs in the Established Choriocarcinoma Cell Lines

Kim, Pan Jo; Lim, Hyun Chul; Kim, Dae Won; Lee, Yoon Soon

Abstract

OBJECTIVE
Taxol (Bristol-Myers Squibb)(paclitaxel) has been shown to be a potent inhibitor of cell growth for a variety of tumors. The aim of this study was to evaluate the interaction of five different combinations of drugs: taxol and cisplatin, topotecan, actinomycin D, methotrexate, and etoposide in two established choriocarcinoma cancer cell lines to identify potential synergistic combinations of chemotherapy for patients with choriocarcinoma.
METHODS
Six antitumor drugs were tested for synergism and antagonism in combination studies using human choriocarcinoma cell lines, JAR and BeWo. Cytotoxic effects were determined by 3-(4,5- dimethylthiazol-2-ly)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Synergic interactions were determined by the median effect principle in which Combination lndex (CI) of less than one suggest a synergic interaction.
RESULTS
Proliferation of JAR and BeWo cells was inhibited by taxol and 2.7 to 86 nmol/L was needed to achieve 50% growth reduction. Combination effect of taxol/cisplatin (fixed ratio of 8 nM: 0.8 ug and 333 nM: 0.8 ug) and taxol/actinomycin-D (fixed ratio of 8 nM: 0.17 nM and 300 nM: 0.003 nM) in JAR and BeWo cell lines showed a synergistic effect at the intermediate and high level of cytotoxicity in both cell lines. Combination effect of taxol/topotecan at all fixed ratio of 8 nM: 1.7 ug showed a synergistic effect at the intermediate and high level of cytotoxicity in JAR cell line. Combination effect of taxol/etoposide at fixed ratio of 8 nM: 0.83 ug and 333 nM: 1.67 ug in JAR and BeWo cell lines showed an antagonistic effect at all level of cytotoxicity in both cell lines.
CONCLUSION
These results suggest that taxol is synergistic with cisplatin, actinomycin-D in both cell lines tested and synergistic with topotecan, methotrexate in one cell line. However the most active drug against trophoblastic disease, etoposide, was antagonistic with taxol in both cell lines. Clinical trials using taxol/ cisplatin or taxol/topotecan combination are warranted to determine whether there is a survival advantage in refractory choriocarcinoma or high risk group and a survival can be achieved with taxol in combination with these drugs.