The emergence of multidrug resistance (MDR) is a significant challenge in breast carcinoma chemotherapy. Kokusaginine isolated from Dictamnus dasycarpus Turcz. has been reported to show cytotoxicity in several human cancer cell lines including breast cancer cells MCF-7. In this study, kokusaginine showed the potent inhibitory effect on MCF-7 multidrug resistant subline MCF-7/ADR and MDA-MB-231 multidrug resistant subline MDA-MB-231/ADR. Kokusaginine markedly induced apoptosis in a concentration-dependent manner in MCF-7/ADR cells. Furthermore, kokusaginine reduced P-gp mRNA and protein levels, and suppressed P-gp function especially in MCF-7/ADR cells. In addition, kokusaginine showed to inhibit tubulin assembly and the binding of colchicine to tubulin by binding directly to tubulin and affects tubulin formation in vitro. Taken together, these results support the potential therapeutic value of kokusaginine as an anti-MDR agent in chemotherapy for breast carcinoma.

多药耐药性（MDR）的出现是乳腺癌化疗中的重大挑战。从Dictamnus dasycarpus Turcz分离出的Kokusaginine 。据报道在包括乳腺癌细胞MCF-7在内的几种人类癌细胞系中显示出细胞毒性。在这项研究中，kokusaginine显示了对MCF-7多药耐药亚系MCF-7 / ADR和MDA-MB-231多药耐药亚系MDA-MB-231 / ADR的有效抑制作用。Kokusaginine在MCF-7 / ADR细胞中以浓度依赖性方式显着诱导凋亡。此外，kokusaginine降低了P-gp mRNA和蛋白质水平，并抑制了P-gp功能，尤其是在MCF-7 / ADR细胞中。另外，kokusaginine通过直接与微管蛋白结合，抑制微管蛋白的组装和秋水仙碱与微管蛋白的结合，并在体外影响微管蛋白的形成。综上所述，这些结果支持了厚朴精氨酸作为抗MDR剂在乳腺癌化疗中的潜在治疗价值。