Lipoplexes formed at N/P 1/1 by targeted liposomes and cargo (Cy7-labeled siRNA targeting MDR1 mRNA) in vivo efficiently accumulate in tumor (∼15-18% of total amount), and kidneys (71%), and were retained there for more than 24 h, causing efficient downregulation of p-glycoprotein expression (to 40% of control) in tumors.
In this study, a plasmid DNA which expressed small hairpin RNA of PD-L1 (shPD-L1) was loaded in the ultrasensitive pH triggered charge/size dual-rebound P[(GP)D] nanoparticles (NPs) to silence the PD-L1 gene for reducing the PD-L1/PD-1 interactions between tumors and T cells.
We transduced CD34+ cells of nine tumor patients with the retroviral SF-MDR vector containing the human multidrug resistance 1 (MDR1) gene under serum-free conditions on the fibronectin fragment CH-296 with or without SCM.
Next-generation taxoids, such as SB-T-1214, are highly potent cytotoxic agents that exhibit remarkable efficacy against drug-resistant tumors in vivo, including those that overexpress the P-glycoprotein (Pgp) efflux pump.
MDR1/P-gp expression and the function of the P-gp pump were investigated in 61 tumor samples from patients with primary breast cancers by multiparameter analysis using MDR1-RT-PCR, immunohistochemistry with two MAbs (UIC2 and MRK16) and the rhodamine 123 (Rh123) efflux assay.
We analyzed the C3435T SNP in the MDR1 gene which is associated with altered cellular drug uptake in matched tumor and normal tissues of 45 patients suffering from colorectal carcinoma.
Tumors with higher tumor margin scores were more strongly associated with the doxorubicin resistance transcriptional program and had a greater prevalence of venous invasion and worse stage.
The immunodetection of the distinct products of the mdr gene family in normal and malignant cells and tissues has greatly contributed to the understanding of the physiological role of P-glycoprotein and its possible involvement in the refractory of tumors to chemotherapy.
TPGS can inhibit P-glycoprotein, enhance drug absorption, induce mitochondrial-associated apoptosis or other apoptotic pathways, promote drug penetration and tumor accumulation, and even inhibit tumor metastasis.
We have identified also 12 different germline polymorphisms and at least two of them were significantly associated with increased lymphoid infiltration in tumors suggesting physiological function for P-gp in immune response in addition to protection from xenobotics.
In reverse transcription-polymerase chain reaction (RT-PCR) analysis, the low inhibitory effect of P-gp modulators in aggressive NK cell tumors did not correlate to the expression level of MDR1 gene, multidrug resistance-associated protein gene, or human canalicular multispecific organic anion transporter gene.
Kaplan-Meier analysis of event free survival for stage 4 tumors revealed a weak trend of inferior survival for patients with Pgp positive tumors (log-rank analysis: P = 0.069).
To identify candidate gene(s) amplified in these tumours, we performed a Southern blot analysis of tumour DNA using probes for 23 known protooncogenes and the multidrug resistance gene, PGY1.
Importantly, ibrutinib could effectively enhance paclitaxel-induced inhibition on the growth of ABCB1- and ABCC10-overexpressing tumors in nude athymic mice.
Renal cell carcinoma (RCC) ranks among the most chemoresistant tumors, and P-glycoprotein (P-gp) predominates multidrug resistance mechanisms by reducing the accumulation of intracellular chemotherapy drugs such as vinblastine (VBL), which is considered the most effective chemotherapeutic agent for this neoplasia.
Also anticancer drugs that belong structurally to classes of drugs extruded from cells by P-gp but that are not substrates of this drug transporter may act as potent inhibitors of MDR tumors (e.g. epothilones, second generation taxanes).
The MDR1-shRNA2 transfected cells showed that the sensitivities to chemotherapy drugs were higher than other shRNAs transfected A2780 cells, and that the formed tumor in mice grew slower than those of other mice after paclitaxel was injected into tumor-bearing nude mice.
The P-glycoprotein (<i>ABCB1</i>/<i>MDR1</i>)-overexpressing CEM/ADR5000 cell line displayed remarkable hypersensitivity to nimbolide, which was mediated through upregulation of the tumor suppressor, PTEN, and its downstream components resulted in significant downregulation in <i>ABCB1</i>/<i>MDR1</i> mRNA and P-glycoprotein.
In this study, the effect of MDR-1 gene silencing, using small interfering RNA (siRNA), and paclitaxel (PTX) co-therapy in overcoming tumor multidrug resistance was examined.