Potency of non-steroidal anti-inflammatory drugs in chemotherapy

Cancer cell resistance, particularly multidrug resistance (MDR), is the leading cause of chemotherapy failure. A number of mechanisms involved in the development of MDR have been described, including the overexpression of ATP-dependent membrane-bound transport proteins. The enhanced expression of these proteins, referred to as ATP-binding cassette (ABC) transporters, results in an increased cellular efflux of the cytotoxic drug, thereby reducing its intracellular concentration to an ineffective level. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently consumed drugs worldwide. NSAIDs are mainly used to treat pain, fever and inflammation. Numerous studies suggest that NSAIDs also show promise as anticancer drugs. NSAIDs have been shown to reduce cancer cell proliferation, motility, angiogenesis and invasiveness. In addition to these effects, NSAIDs have been shown to induce apoptosis in a wide variety of cancer types. Moreover, several studies have indicated that NSAIDs may sensitise cancer cells to the antiproliferative effects of cytotoxic drugs by modulating ABC transporter activity. Therefore, combining specific NSAIDs with chemotherapeutic drugs may have clinical applications. Such treatments may allow for the use of a lower dose of cytotoxic drugs and may also enhance the effectiveness of therapy. The objective of this review was to discuss the possible role of NSAIDs in the modulation of antitumour drug cytotoxicity. We particularly emphasised on the use of COX-2 inhibitors in combination with chemotherapy and the molecular and cellular mechanisms underlying the alterations in outcome that occur in response to this combination therapy.