Hypocrellin B triggered sonodynamic therapy reverses multidrug resistance of doxorubicin-resistant SGC7901/ADR cells via down-regulation of P-gp expression

Abstract

The combating of multidrug resistance (MDR) plays a crucial role in effective chemotherapy. However, current strategies for cancer of MDR remain unsatisfactory for their limited efficacy and severe side effects. In this study, we sought to determine the anti-MDR effects of a traditional chinese herb, Hypocrellin B (HB)-mediated sonodynamic therapy (HB-SDT) on human gastric multidrug resistance cancer SGC-7901cell/ADR cells and its underlying mechanisms. HB-SDT can synergistically increase the cytotoxicity of DOX on SGC-7901cell/ADR cells in which the mechanism is related to significant promotion of apoptosis, ROS level and drop of MMP in the resistant cells after combining treatment of DOX and HB-SDT. Meanwhile, western blotting assays display the expression of apoptosis related proteins Bax and Bcl-2 changed markedly after the combination treatment. In addition, the expression of P-gp was significantly down-regulated after treatment of HB-SDT and DOX. HB-SDT can increase DOX-induced mitochondrial-dependent apoptosis by inhibiting the expression of P-gp, thereby increasing the cytotoxic effect into SGC7901/ADR cells.

Keywords:

• Hypocrellin B
• sonodynamic therapy
• multidrug resistance
• DOX
• P-gp protein

Disclosure statement

The authors have declared that no competing interest exists.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (81872497), and the Fundamental Research Funds for the Central Universities (2016TS056).

Notes on contributors

Yichen Liu

Yichen Liu, Doctor candidate, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China. All authors are all part of a research team, which, led by Dr. Pan Wang, has spent years studying the effect of sonodynamic therapy in the anticancer field, as well as the study of the targeted delivery of activating tumor therapeutic drugs and the underlining mechanism.

Hong Bai

Hong Bai, Master, Medical College, Xi’an Peihua University, Xi’an 710125, Shaanxi, China. Work in biochemistry and molecular biology research.

Kaili Guo

Kaili Guo, Master candidate, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China.

Pan Wang

Pan Wang, Doctor, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, China. He is interested in targeted drug delivery and its precise treatment in sonodynamic therapy.