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

Abstract Glioblastoma (GBM) has high mortality rates because of extremely therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) is an emerging and promising approach combined with low-intensity ultrasonication (US) and PpIX as a sonosensitizer for cancer, whereas its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, a MDR1 inhibitor and augmented anti-tumor effects of SDT. MDR1 down-regulation via Akt/NF-kB pathway by celecoxib was confirmed, using a NF-kB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via Akt/NF-kB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

Download Full-text

Down-Regulation of miR-27a Might Reverse Multidrug Resistance of Esophageal Squamous Cell Carcinoma

Digestive Diseases and Sciences ◽

10.1007/s10620-009-1051-6 ◽

2009 ◽

Vol 55 (9) ◽

pp. 2545-2551 ◽

Cited By ~ 88

Author(s):

Hongwei Zhang ◽

Mengbin Li ◽

Yu Han ◽

Liu Hong ◽

Taiqian Gong ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Multidrug Resistance ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Down Regulation

Download Full-text

Shiga-Like Toxin II Impairs Hepatobiliary Transport of Doxorubicin in Rats by Down-Regulation of Hepatic P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.5.1636-1642.2003 ◽

2003 ◽

Vol 47 (5) ◽

pp. 1636-1642 ◽

Cited By ~ 27

Author(s):

Kazuhiko Hidemura ◽

Ying Lan Zhao ◽

Katsuki Ito ◽

Akimasa Nakao ◽

Yasuaki Tatsumi ◽

...

Keyword(s):

Multidrug Resistance ◽

Biliary Excretion ◽

Histopathological Examination ◽

Total Concentration ◽

Down Regulation ◽

Unbound Fraction ◽

Biliary Clearance ◽

Hepatobiliary Transport ◽

P Glycoprotein ◽

Tnf Α

ABSTRACT We investigated the effect of Shiga-like toxin II (SLT-II), derived from Escherichia coli O157:H7, on the hepatobiliary excretion of doxorubicin, a substrate for P glycoprotein and the multidrug resistance-associated protein Mrp2, and on the expression of P glycoprotein and Mrp2 in rats. Histopathological examination did not show any liver injury in SLT-II-treated rats. A significant delay in the disappearance of doxorubicin from plasma after its intravenous administration (5 mg/kg of body weight) was observed in rats treated 24 h earlier with SLT-II (2 μg/animal). When rats received an infusion of doxorubicin (2.6 μg/min) 24 h after intravenous injection of SLT-II, the steady-state concentration of doxorubicin in plasma increased and the bile flow decreased, whereas the concentration in liver did not alter. SLT-II significantly increased the unbound fraction of doxorubicin in plasma but did not alter the concentration in liver tissue. SLT-II significantly decreased the biliary excretion rate and biliary clearance of doxorubicin based on the total concentration and concentration of the unbound fraction in plasma and liver. Western blot analysis revealed that SLT-II down-regulated P glycoprotein and Mrp2 in the liver, which could explain the observed decrease in the biliary excretion of doxorubicin by SLT-II. A tumor necrosis factor alpha (TNF-α) production inhibitor, pentoxifylline, could not protect SLT-II-induced decreases in the biliary clearance of doxorubicin and down-regulation of both transporters. It is unlikely that TNF-α plays a major role in the SLT-II-induced decrease in the hepatobiliary transport of doxorubicin and the down-regulation of both transporters.

Download Full-text