Tags

Type your tag names separated by a space and hit enter

Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells.
Pathol Res Pract. 2017 Jul; 213(7):848-853.PR

Abstract

Multidrug resistance (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene is major obstacles for successful cancer chemotherapy. P-gp could extrude anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. MDR reversal agents for P-gp can restore the sensitivity of MDR cells to such drugs. Saikosaponin D (SSd), one of the major triterpenoid saponins derived from Bupleurum chinense DC (BCDC), has been shown to possess anti-inflammatory, anti-infectious and anti-tumor properties. The aim of the present study was to investigate the reversal effect of SSd on MDR in MCF-7/adriamycin (ADR) human breast cancer cells and investigate the underlying mechanisms of SSd. The results demonstrated that SSd inhibited the proliferation of MCF-7/ADR and MCF-7 cells in a dose-dependent manner. Moreover, SSd increased the cytotoxicity of ADR on MCF-7/ADR cells and the resistance fold of SSd treatment was demonstrated to be significantly higher when compared with that of the group without SSd treatment. Additionally, the effects of the drug combination showed that SSd and ADR combination were synergistic. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that SSd restored Rh123 accumulation and inhibited P-gp-mediated drug efflux. Importantly, we found that SSd could enhance the sensitivity of MCF-7/ADR cells towards ADR by down-regulating MDR1 and P-gp expression. In conclusion, the results of the present study indicated that SSd may represent a potent reversal agent for P-gp-mediated MDR in breast cancer therapy.

Authors+Show Affiliations

Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China.Life Science Research Center, Beihua University, Jilin, Jilin 132013, People's Republic of China.Department of Surgery, Affiliated Hospital of Beihua University, Jilin, Jilin 132013, People's Republic of China.Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China.Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China.Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, Jilin 132013, People's Republic of China. Electronic address: bhdxgaixiaodong@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28554760

Citation

Li, Chun, et al. "Reversal of P-glycoprotein-mediated Multidrug Resistance Is Induced By Saikosaponin D in Breast Cancer MCF-7/adriamycin Cells." Pathology, Research and Practice, vol. 213, no. 7, 2017, pp. 848-853.
Li C, Guan X, Xue H, et al. Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells. Pathol Res Pract. 2017;213(7):848-853.
Li, C., Guan, X., Xue, H., Wang, P., Wang, M., & Gai, X. (2017). Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells. Pathology, Research and Practice, 213(7), 848-853. https://doi.org/10.1016/j.prp.2017.01.022
Li C, et al. Reversal of P-glycoprotein-mediated Multidrug Resistance Is Induced By Saikosaponin D in Breast Cancer MCF-7/adriamycin Cells. Pathol Res Pract. 2017;213(7):848-853. PubMed PMID: 28554760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells. AU - Li,Chun, AU - Guan,Xingang, AU - Xue,Haogang, AU - Wang,Peng, AU - Wang,Manli, AU - Gai,Xiaodong, Y1 - 2017/02/03/ PY - 2016/10/10/received PY - 2017/01/26/revised PY - 2017/01/26/accepted PY - 2017/5/31/pubmed PY - 2018/4/3/medline PY - 2017/5/31/entrez KW - Breast cancer KW - MDR1 KW - Multidrug resistance KW - P-glycoprotein KW - Saikosaponin D SP - 848 EP - 853 JF - Pathology, research and practice JO - Pathol Res Pract VL - 213 IS - 7 N2 - Multidrug resistance (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene is major obstacles for successful cancer chemotherapy. P-gp could extrude anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. MDR reversal agents for P-gp can restore the sensitivity of MDR cells to such drugs. Saikosaponin D (SSd), one of the major triterpenoid saponins derived from Bupleurum chinense DC (BCDC), has been shown to possess anti-inflammatory, anti-infectious and anti-tumor properties. The aim of the present study was to investigate the reversal effect of SSd on MDR in MCF-7/adriamycin (ADR) human breast cancer cells and investigate the underlying mechanisms of SSd. The results demonstrated that SSd inhibited the proliferation of MCF-7/ADR and MCF-7 cells in a dose-dependent manner. Moreover, SSd increased the cytotoxicity of ADR on MCF-7/ADR cells and the resistance fold of SSd treatment was demonstrated to be significantly higher when compared with that of the group without SSd treatment. Additionally, the effects of the drug combination showed that SSd and ADR combination were synergistic. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that SSd restored Rh123 accumulation and inhibited P-gp-mediated drug efflux. Importantly, we found that SSd could enhance the sensitivity of MCF-7/ADR cells towards ADR by down-regulating MDR1 and P-gp expression. In conclusion, the results of the present study indicated that SSd may represent a potent reversal agent for P-gp-mediated MDR in breast cancer therapy. SN - 1618-0631 UR - https://www.unboundmedicine.com/medline/citation/28554760/Reversal_of_P_glycoprotein_mediated_multidrug_resistance_is_induced_by_saikosaponin_D_in_breast_cancer_MCF_7/adriamycin_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0344-0338(16)30521-0 DB - PRIME DP - Unbound Medicine ER -