Dual inhibition of P-glycoprotein and midkine may increase therapeutic effects of anticancer drugs

• Published in: Medical hypotheses 2017-09, Vol.107, p.26-28
• Main Authors: Aynacıoğlu, A. Şükrü, Bilir, Ayhan, Kadomatsu, Kenji
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - genetics; Gene Expression; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Models, Biological; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Proteins - antagonists & inhibitors
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2017.07.019

Multidrug resistance (MDR) to chemotherapy may significantly affect the outcome of cancer treatment. ATP-dependent drug efflux pumps, including P-glycoprotein (P-gp), contribute to the resistance of various chemotherapeutic agents. Overexpression of P-gp in tumor cells induces chemoresistance via pumping the anticancer drugs out of the cells. In addition to taking part in many biological processes such as development, reproduction and repair, midkine (MK) also plays important roles in the pathogenesis of malignant diseases as well as in the regulation of MDR. Although, the mechanisms of action of P-gp and MK are different, overexpression of both proteins prevents the accumulation of many chemotherapeutics in tumor cells, leading to decreased therapeutic effects of anticancer drugs. Therefore, identification of the result of dual inhibition of P-gp and MK in overcoming chemoresistance may enhance the likelihood for a more efficient chemotherapy.