Background: Hepatoma is a common malignancy in the world with high morbidity and mortality. The treatment
of hepatoma is limited by its poor response to many chemotherapeutic agents. Although paclitaxel (PTX) is widely used in
clinical chemotherapy, the low sensitivity to hepatoma restricts its application. Combination therapy is a promising approach
to resolve this dilemma.
Objective: To evaluate the interaction between paclitaxel, bufalin (BFL) and cinobufagin (CBF), and explore the optimum
Methods: HepG2 cells were treated with PTX, BFL and CBF individually or in combination. Their interactions were evaluated by two classical models (Chou-Talalay model and Bliss independence). Response surface methodology (RSM) was
used to explore the optimum combination. Furthermore, the optimum drug combination was verified by the morphological
Results: Synergistic effects were observed when cells were exposed to binary mixtures of PTX+CBF and BFL+CBF. Although the interaction of PTX and BFL was summative, strong synergistic effect was observed when cells were exposed to
ternary mixtures of PTX+BFL+CBF. The interaction results of RSM were consistent with classical models, but more efficient. Moreover, the optimum combination dose was given by RSM without the combinatorial explosion of exhaustive testing.
Conclusion: The combination of BFL and CBF synergistically enhanced the potency of PTX against HepG2 cells. RSM
could give an accurate evaluation for drug interactions and efficient prediction of optimum combination.