Abstract: Objective Investigate anticancer effects and mechanisms of o-nitrobenzyl-isatinyl chalcone (ONIC) used alone or in drug combination. Method Detection of proliferation inhibition on cultured cancer cells treated with ONIC. Using Chou’s and Jin’s methods to evaluate drug combination effects among ONIC and ten anticancer drugs or pathway inhibitors. Result ONIC had potent in vitro anticancer activity against eight cancer cell lines. Five drugs were shown to have synergetic effects with ONIC: HSP 90 inhibitor 17-AAG, Arf inhibitor brefeldin A, proteasome inhibitor bortezomib, mTOR inhibitor rapamycin, and ERK1/2 inhibitor U0126. Antagonistic effects were revealed among ONIC and three drugs: RhoA inhibitor fasudil, PI3K inhibitor LY294002, and LKB1-AMPK agonist metformin. Both the microtubule stabilizer paclitaxel and Rac1 inhibitor NSC23766 showed additive effects with ONIC. Conclusion ONIC not only itself has potent anticancer activity, but also has specific synergetic or antagonistic effects in combination with other drugs, suggesting that the RhoA pathway and the up- and downstream elements in mTOR pathway were closely related with the anticancer mechanisms of ONIC.

Key words: Key words: isatin, chalcone, anticancer drugs, synergy, drug combination