PURPOSE: ET-743 (Yondelis, trabectedin) and PM00104 (Zalypsis) are marine derived compounds which demonstrate anti-tumor activity. The present study was performed to elucidate the relationship between the expression of ABCB1/MDR1 and ABCC1/MRP1 with resistance to either ET-743 or PM00104. METHODS: We evaluate the association between expression of Pgp1, MRP1, and BCRP proteins and ET-743 or PM00104 resistance in a large panel of multi-drug resistant cell lines derived from histologically unrelated human tumors that were selected with paclitaxel, doxorubicin, cisplatin, mitoxantrane, or gemcitibine. RESULTS: Paclitaxel selected resistant cell lines expressed high levels of ABCB1 (but not ABCC1 or ABCG2/BCRP) did not demonstrate cross-resistance to either ET-743 or PM00104. In contrast, the doxorubicin selected resistant cell lines also expressed high level of ABCB1 (but not ABCC1 or ABCG2) but did demonstrate significant cross-resistance to both ET-743 and PM00104. The paclitaxel selected cell lines demonstrated cross-resistance to doxorubicin, vincristine, and mitoxantrane, while most of the above doxorubicin selected cell lines demonstrated cross-resistance to paclitaxel and vincristine, but not to mitoxantrane. On the contrary, cisplatin and gemcitabine selected cell lines demonstrated no cross-resistance to paclitaxel, doxorubicin, ET-743, or PM00104. siRNA down-regulation of ABCB1 expression in doxorubicin selected cell lines caused partial sensitization to both doxorubicin and paclitaxel but not to either ET-743 or PM00104. CONCLUSIONS: These results indicate that cell lines selected for resistance to either paclitaxel or doxorubicin are cross-resistant to many other drugs and that, for these cell lines, ABCB1 over-expression is not necessary to confer resistance to either ET-743 or PM00104. Diversity of cross-resistance observed in these multi-drug resistant cell lines are associated with the initial drug used for in vitro selection, but not to ABCB1 expression. This study suggests that a common molecular pathway other than ABCB1 may be involved in the mechanism of resistance to ET-743 or PM00104.
PURPOSE:ET-743 (Yondelis, trabectedin) and PM00104 (Zalypsis) are marine derived compounds which demonstrate anti-tumor activity. The present study was performed to elucidate the relationship between the expression of ABCB1/MDR1 and ABCC1/MRP1 with resistance to either ET-743 or PM00104. METHODS: We evaluate the association between expression of Pgp1, MRP1, and BCRP proteins and ET-743 or PM00104 resistance in a large panel of multi-drug resistant cell lines derived from histologically unrelated humantumors that were selected with paclitaxel, doxorubicin, cisplatin, mitoxantrane, or gemcitibine. RESULTS:Paclitaxel selected resistant cell lines expressed high levels of ABCB1 (but not ABCC1 or ABCG2/BCRP) did not demonstrate cross-resistance to either ET-743 or PM00104. In contrast, the doxorubicin selected resistant cell lines also expressed high level of ABCB1 (but not ABCC1 or ABCG2) but did demonstrate significant cross-resistance to both ET-743 and PM00104. The paclitaxel selected cell lines demonstrated cross-resistance to doxorubicin, vincristine, and mitoxantrane, while most of the above doxorubicin selected cell lines demonstrated cross-resistance to paclitaxel and vincristine, but not to mitoxantrane. On the contrary, cisplatin and gemcitabine selected cell lines demonstrated no cross-resistance to paclitaxel, doxorubicin, ET-743, or PM00104. siRNA down-regulation of ABCB1 expression in doxorubicin selected cell lines caused partial sensitization to both doxorubicin and paclitaxel but not to either ET-743 or PM00104. CONCLUSIONS: These results indicate that cell lines selected for resistance to either paclitaxel or doxorubicin are cross-resistant to many other drugs and that, for these cell lines, ABCB1 over-expression is not necessary to confer resistance to either ET-743 or PM00104. Diversity of cross-resistance observed in these multi-drug resistant cell lines are associated with the initial drug used for in vitro selection, but not to ABCB1 expression. This study suggests that a common molecular pathway other than ABCB1 may be involved in the mechanism of resistance to ET-743 or PM00104.
Authors: X Yang; P Yang; J Shen; E Osaka; E Choy; G Cote; D Harmon; Z Zhang; H Mankin; F J Hornicek; Z Duan Journal: Br J Cancer Date: 2014-05-22 Impact factor: 7.640
Authors: Victoria Moneo; Beatriz G Serelde; Carmen Blanco-Aparicio; Ramon Diaz-Uriarte; Pablo Avilés; Gemma Santamaría; Juan C Tercero; Carmen Cuevas; Amancio Carnero Journal: BMC Cancer Date: 2014-04-23 Impact factor: 4.430
Authors: Zhenfeng Duan; Edwin Choy; David Harmon; Cao Yang; Keinosuke Ryu; Joseph Schwab; Henry Mankin; Francis J Hornicek Journal: PLoS One Date: 2009-09-09 Impact factor: 3.240
Authors: Anna Małek; Bartłomiej Taciak; Katarzyna Sobczak; Agnieszka Grzelak; Michał Wójcik; Józef Mieczkowski; Roman Lechowski; Katarzyna A Zabielska-Koczywąs Journal: Molecules Date: 2021-06-08 Impact factor: 4.411