Synergistic anticancer mechanisms of curcumol and paclitaxel in triple-negative breast cancer treatment may involve down-regulating ZBTB7A expression via the NF-B signaling pathway

Abstract

Objectives: This study aimed to verify whether curcumol combined with paclitaxel exerted synergistic antiproliferative and proapoptotic effects in MDA-MB-231 mammary cancer cells.

Materials and methods: The effects of different concentrations of CC, PTX, and their combination on the proliferation of MDA-MB-231 mammary cancer cells were determined by CCK-8 laboratory tests. Combination index (CI) was calculated using CompuSyn software. Colony formation assays, Hoechst 33258 immunofluorescence staining, and flow cytometry were carried out to observe proliferation and apoptosis in each group. The protein expression of PCNA, Bcl-2, Bax, ZBTB7A, p-p65, and NF-ƙB p65 was detected by western blotting. The xenograft tumor volume and body mass of nude mice were measured. Immunohistochemistry was used to detect the expression of PCNA , NF-B p65 and ZBTB7A. TUNEL and DAPI staining were used to detect the apoptosis of tumor cells.

Results: Curcumol combined with paclitaxel exerted a significant inhibitory effect on proliferation of MDA-MB-231 cells in the CCK-8 laboratory test. Hoechst 33258 immunofluorescence staining, flow cytometry, TUNEL, and DAPI apoptosis staining demonstrated that cell apoptosis was the highest in the CC+PTX group in vivo and in vitro. Expression of PCNA, Bcl-2, ZBTB7A, p-p65, and NF-B p65 was lowest in the CC+PTX group, while the expression of Bax was highest. The growth of xenograft tumors in the CC+PTX group was most notably suppressed. Immunohistochemistry showed that expression of PCNA, ZBTB7A, and NF-ƙB p65 was the lowest in the CC+PTX group.

Conclusion: Curcumol combined with paclitaxel exerted a synergistic antiproliferative and proapoptotic effect on triple-negative breast cancer cells.

Keywords: Curcumol; NF-Ƙb; Paclitaxel; TNBC; ZBTB7A.

Figure 1

CC and PTX restrained the viability of MDA-MB-231 cells. CC combined with PTX had a synergistic effect on suppressing the viability of MDA-MB-231 cells

Figure 2

CC combined with PTX restrained colony formation of MDA-MB-231 cells

Figure 3

CC combined with PTX promoted apoptosis and morphological changes of MDA-MB-231 cells

Figure 4

Protein expression of PCNA, Bcl-2, Bax, ZBTB7A, p-p65, and p65 in each group of MDA-MB-231 cells

Figure 5

Effects of curcumol combined with paclitaxel on proliferation of MDA-MB-231 cells in vivo

Figure 6

Effects of curcumol combined with paclitaxel on expression of PCNA, ZBTB7A, and p65 in xenograft tumor tissues by immunohistochemistry (×400)

Figure 7

Effects of curcumol combined with paclitaxel on apoptosis of MDA-MB-231 cells in vivo (×200)