Huaier extract enhances the treatment efficacy of paclitaxel in breast cancer cells via the NF-[KAPPA]B/I[KAPPA]B[alpha] pathway

Breast cancer is considered as the most common malignant disease in women. Huaier extract, a type of traditional Chinese medicine, has been found to have antitumor activity. In the present study, we aimed to investigate whether the combined treatments of paclitaxel and Huaier extract may improve treatment efficacy in breast cancer cells. Human breast cancer cell lines MCF-7 and MDA-MB-231 were used to evaluate the antitumor efficacy of Huaier extract and paclitaxel both in vitro and in vivo. Using proliferation assays and flow cytometry, we found that both Huaier extract and paclitaxel decreased cell viability and induced cell apoptosis in a time- and dose-dependent manner. The combined treatments were more effective than monotherapy. Huaier extract induced cycle arrest in the G0/G1 phase, and paclitaxel arrested the cell cycle in the G2/M phase. Furthermore, the results of real-time PCR and western blotting revealed that Huaier extract decreased p65 and c-Met expression and increased I[KAPPA]B[ALPHA] expression, while paclitaxel increased p65 expression and reduced I[KAPPA]B[alpha] and c-Met expression. Consistent with the in vitro results, both Huaier extract and paclitaxel exerted a significant inhibitory effect on xenografted tumor growth, and the combined therapies revealed the most marked inhibitory effect. Collectively, our results indicated that Huaier extract increased the antitumor effect of paclitaxel therapy in breast cancer cells. The molecular mechanisms may be involved in the inhibition of the NF-[KAPPA]B pathway and c-Met expression.