Hyaluronan Mediated Enhanced Chemotherapeutic Activity

Multidrug resistance is an intrinsic problem in cancer chemotherapy. Unfortunately, as therapy has become more and more effective, acquired resistance has also become common (90). The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more Adenosine triphosphate (ATP)-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance, including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms, probably play an important role in drug resistance (91-97).

HA has been shown to produce synergistic therapeutic effects when coadmi-nistered with 5-fluorouracil (5-FU) and with PTX. HA formulated with 5-FU enhanced the cellular uptake and cytotoxicity of the drug compared to unformu-lated 5-FU (98). A similar effect has been observed when PTX was coadministered with HA (99). The admixture of PTX and HA significantly reduced the migration of Lewis lung carcinoma cells in a synergistic fashion and markedly improved the life span of mice seeded with tumor cells compared with PTX alone or HA alone.

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