P-glycoprotein Mitochondrial Translocation on Multidrug Resistance in the Mitochondrial DNA-depleted Cells

Abstract: Cells that express the multidrug resistance (MDR) phenotype are resistant to the mitochondrial related apoptosis induced by several anticancer drugs. Why the mitochondrial DNA depleted cells showed MDR phenotype is still unknown. This study focused on P-glycoprotein (P-gp) mitochondrial translocation on multidrug resistance in the mitochondrial DNA-depleted cells. SK-Hep1， ρ0SK-Hep1 and the transmitochondria cells SKHep1Cyb were used. Sensitivity of the cells to chemotherapeutic drugs was assessed by CCK-8 assays. Apoptosis ratio of the cells were measured by Annexin V/PI double staining. Expression of P-gp was detected by Western blot， and distribution of P-gp within the cells was assayed by immunofuorescence combined with laser scanning confocal microscopy. Results showed， the IC50 of SK-Hep1， ρ0SK-Hep1 and SK-Hep1Cyb to Doxorubicin were 0.62±0.02 μg/ml， 4.93±0.17 μg/ml and 0.57±0.02 μg/ml， respectively， and the apoptosis ratio of SK- Hep1， ρ0SK-Hep1 and SK-Hep1Cyb were 11.25%±1.36%、4.75%±0.98% and 14.50%±1.57%， respectively. The ρ0SKHep1 exhibited resistance to apoptosis induced by the chemotherapeutic drugs. P-gp、Bax and Bcl-2 were overexpressed and Bcl-2/Bax increased. ρ0 cells showed resistance to apoptosis induced by chemotherapeutic drugs， and this might be related to increased Bax/Bcl-2， and increased P-gp translocation to mitochondria in the ρ0 cells. Therefore， P-gp could be involved in the protection of apoptosis due to antiproliferative drugs.

CSTR: 32200.14.cjcb.2011.01.0006