Although the remarkable anti-cancer propensity of silver nanoparticles (AgNP) has been demonstrated and their potential application in MDR cancer has been proposed, the nanoparticle size-dependent cellular events directing P-glycoprotein (Pgp) expression and activity in MDR cancer have never been addressed.
Therefore, studies on the interaction between artemisinin derivatives and P-gp provide important information for the development of novel anti-cancer artemisinin derivatives to reverse P-gp mediated MDR and for the design of rational artemisinin-based combination therapies against cancer.
Among all members in ABC transporters superfamily, ABCB1 (ABC transporter subfamily B #1) and ABCG2 (ABC transporter subfamily G #2) play an important role in the development of cancer MDR.
The ATP-binding cassette subfamily B member 1 (ABCB1) multidrug transporter P-glycoprotein plays a central role in clearance of xenobiotics in humans and is implicated in cancer resistance to chemotherapy.
We hypothesised that these hallmarks were due to the presence of a sub-population of cancer stem cells expressing the multi-drug efflux transporter ABCB1.
Overexpression of efflux transporters of the ATP-binding cassette (ABC) transporter family, primarily P-glycoprotein (P-gp), is a frequent cause of multidrug resistance in cancer and leads to failure of current chemotherapies.
The impact of P-gp expression on anticancer drug efficacy was assessed by using five colon cancer cell lines expressing varying endogenous P-gp levels and by selecting from the Cancer Cell Line Encyclopedia (CCLE). mRNA expression of MDR1 was considered as a surrogate of the protein expression of its gene product, P-gp, in CL-11, C2BBe1 and RKO cells, whereas P-gp protein expression in plasma membranes or crude membrane fractions was lower than expected from mRNA expression in CW-2 and CL-40 cells.
Moreover, up-regulation of MTDH gene significantly increased the gene expression of MDR1, Snail and NF-κB p65, deceased the gene expression of E-cadherin, enhanced cell proliferation, and anaerobic glycolysis and activated transformation into cancer stem cells.
Tetrandrine Interaction with ABCB1 Reverses Multidrug Resistance in Cancer Cells Through Competition with Anti-Cancer Drugs Followed by Downregulation of ABCB1 Expression.
Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance.
Benzoxanthone analogue, compound 1 is strongly suggested to be a promising inhibitor of P-gp to improve an oral absorption of compounds for cancer therapy.
Development of agents to overcome multidrug resistance (MDR) is one of the important strategies in cancer chemotherapy, and P-glycoprotein (P-gp) correlates with the degree of resistance.
A great deal of research shows that the occurrence of drug resistance in various malignant tumors is closely related to the expression of P-glycoprotein (P-gp) on the surface of the cell membrane.
The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps.
Moreover, the expression levels of cancer stemness markers (CD44 and CD133) and drug transporter MDR-1 were significantly diminished in rats receiving combined therapy.
These results suggest phthalate exposure enhances colon cancer cell metastasis and chemotherapeutic drug resistance by increasing cancer cell stemness, and that P-glycoprotein inhibitors might improve outcomes for advanced or drug-resistant colon cancer patients.
In the aggregate, newly synthesized MSNP-PEI-DOX/MDR1-siRNA improves cancer chemotherapy effect in terms of treating multidrug-resistant cancer compared to DOX only, clearly demonstrating that MSNP-PEI-DOX/MDR1-siRNA has potential therapeutic application for multidrug-resistant cancer in the future.
The most known ABC transporters are ABCB1 and ABCC1, involved in the multidrug resistance phenotype in cancer, given their participation in cellular detoxification.In <i>T. cruzi</i>, 27 ABC genes were identified in the genome.