Are low molecular weight heparins able to sensitize chemoresistant tumor cells?

Abstract

Venous thromboembolic complications are often associated with malignant diseases. The treatment and prevention of these events in cancer patients is frequently carried out using low-molecular-weight heparin (LMWH). However, heparin has other pharmacological effects in addition to the antithrombotic activities [1], e.g., antimetastatic and antiangiogenetic activities and these are currently subjects of intensive research [2]. In clinical trials with cancer patients it has been shown that treatment with LMWH is associated with an increase in survival rate and this effect of LMWH is not only attributable to its prevention of lethal thromboembolic complications [3]. Recent additional findings show that unfractioned heparin (UFH) can alter the chemoresistance of tumor cells by interference with P-glycoprotein (P-gp)-mediated multidrug resistance [4]. Therefore, it appears worthwhile to investigate whether LMWH acts as a potential synergist or modulator of chemotherapy. However, published data on this topic are rare. The aim of this in vitro study was to obtain an insight into the possible interaction between LMWH and P-gp in multidrug resistant cells and to investigate whether this can be considered as a plausible mechanism explaining the improvement in survival of cancer patients receiving anticoagulant treatment. In this study the influence of the LMWH tinzaparin on Pgp-independent chemoresistance phenomenon such as that associated with cisplatin resistance was also investigated.