Ginsenoside Rh2 pretreatment and withdrawal reactivated the pentose phosphate pathway to ameliorate intracellular redox disturbance and promoted intratumoral penetration of adriamycin.

ABSTRACT: Improving the limited penetration, accumulation and therapeutic effects of antitumor drugs in the avascular region of the tumor mass is crucial during chemotherapy. P-gp inhibitors have achieved little success despite significant efforts. Excessive P-gp inhibition disturbed the kinetic balance between intracellular accumulation and intercellular penetration, thus resulting in a more inhomogeneous distribution of substrate drugs. Here, we found that ginsenoside Rh2 pretreatment mildly downregulated P-gp expression through reactivating the pentose phosphate pathway and rebalancing redox status. This mild P-gp inhibition not only significantly increased the growth inhibition effect and accumulation profile of adriamycin (ADR) throughout the multicellular tumor spheroid (MCTS) but also had uni

SUBMITTER: Liu J 

PROVIDER: S-EPMC7264470 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature