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.