Inhibition of GST-pi nuclear transfer increases mantle cell lymphoma sensitivity to cisplatin, cytarabine, gemcitabine, bortezomib and doxorubicin.

PURPOSE: Mantle cell lymphoma (MCL) is a chemoresistant lymphoma overexpressing the class pi glutathione-S-transferase (GST-pi). The nuclear localisation of GST-pi is induced by chemotherapy and is correlated to cell resistance. In this study, the effect of the Agaricus bisporus lectin (ABL), a GST-pi nuclear transfer inhibitor, on the chemosensitivity of MCL cells was investigated.

METHODS: The proliferation of three MCL cell lines was evaluated in the presence of doxorubicin (DOX), cisplatin (CDDP), cytarabine (Ara-C), gemcitabine (GEM) or bortezomib with or without ABL pre-treatment.

RESULTS: The cytotoxic activities of CDDP, Ara-C, GEM and bortezomib were increased in all cell lines. The DOX cytotoxic activity was enhanced in two of three cell lines. The inhibition of GST-pi nuclear transfer led to the potentialisation of all drug combinations.

CONCLUSION: The inhibition of the nuclear transfer of GST-pi increases the MCL sensitivity to DOX, CDDP, Ara-C, GEM and bortezomib, alone or in combination.