Currently, chemotherapy is still a primary method to treat cancers. Doxorubicin is a regular chemotherapy drug, and a previous study indicated that mPEG5k-b-P(Glu10-r-Phe10)-doxorubicin is a more excellent nanodrug for cancer therapy, as it created a therapeutic advantage compared with free doxorubicin. Therefore, the efficacy of doxorubicin-resistant tumor treatment was investigated in this paper. While the cell viability and cell uptake results did not reflect an advantage of the nanodrug in drug-resistant tumors, comparison of the genetic expression of sensitive and resistant tumor cells highlighted NFκB. The proteasome inhibitor bortezomib, which is approved clinically and may influence the NFκB activity, was thus employed. The MTT assay and flow cytometry indicated that it could increase the therapeutic efficacy of poly(amino acid)-doxorubicin, and Western blot results showed that bortezomib and poly(amino acid)-doxorubicin can synergistically diminish NFκB expression. The synergism was confirmed through the orthotopic xenograft model in vivo. Thus, bortezomib can enhance the cancer therapeutic efficiency of poly(amino acid)-doxorubicin not only during the sensitive period but also during the resistant period. This makes the combination of bortezomib and poly(amino acid)-doxorubicin a potent strategy and guidance for the clinic.
Keywords: NFκB; bortezomib; chemotherapy; multidrug resistance; nanodrug.