To overcome this problem, we constructed a multifunctional DNA origami-based nanocarrier for codelivery of a chemotherapeutic drug (doxorubicin, Dox) and two different antisense oligonucleotides (ASOs; B-cell lymphoma 2 (Bcl2) and P-glycoprotein (P-gp)) into drug-resistant cancer cells for enhanced therapy.
The expression of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-2 associated X (BAX), Ezrin, matrix metalloproteinase 2 (MMP2), lung resistance-related protein (LRP), multiple drug resistance protein 1 (MRP1), glutathione-S-transferase-π (GST-π), and P glycoprotein (P-gp) protein was determined by Western blotting.
The aim of the present study was to elucidate the role of ROS in mediating the effect of SalB on drug resistance and the correlation with drug resistance‑associated protein, P‑glycoprotein (P‑gp), and apoptosis‑associated proteins, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X (Bax).
Preliminary work involved the screening of multidrug resistant (MDR) gene expression, including MDR1, MRP1 and B-cell lymphoma 2 (BCL-2) at the mRNA levels.
Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting.
No statistical differences in the apoptosis rate of A549/DDP cell line in the early stage were found among the three groups (all P > 0.05), but the late-stage apoptosis rate in the anti-miR-196a group was significantly higher than that in the blank group and the miR-NC group (both P < 0.05); The expressions of human multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), excision repair cross-complementation 1 (ERCC1), survivin, and B cell lymphoma 2 (Bcl-2) decreased significantly while RhoE increased significantly in the anti-miR-196a group than the blank group and the miR-NC group (all P < 0.05).
In addition, miR‑10a suppressed the cellular expression of P‑glycoprotein, multi‑drug resistance protein (MDR) 1, MDR‑associated protein 1, RhoE, B cell lymphoma‑2 and survivin in A549/DDP cells.
Western blot analysis and quantitative reverse-transcription polymerase chain reaction (RT-PCR) revealed that cells underexpressing CCND1 exhibited decreased multidrug resistance protein 1 (MDR1) and B-cell lymphoma-2 (Bcl-2) expression, but enhanced apoptosis effector caspase-3 expression.