Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells
作者： Tamara Minko , Elena V. Batrakova , Shu Li , Yili Li , Refika I. Pakunlu
DOI: 10.1016/J.JCONREL.2005.03.019
关键词: Programmed cell death 、 Annexin A5 、 Caspase 3 、 Cancer cell 、 Annexin 、 Apoptosis 、 Pharmacology 、 Biology 、 P-glycoprotein 、 Cytotoxic T cell
摘要: Pluronic block copolymer P85 (P85) sensitizes multidrug resistant (MDR) cancer cells resulting in the increase of cytotoxic activity antineoplastic agents. This effect is attributed to inhibition most clinically relevant drug efflux transporter, P-glycoprotein (Pgp), through combined ATP depletion and Pgp ATPase activity. The present study elucidates effects an anticancer agent, doxorubicin (Dox), formulated with on drug-induced apoptosis MDR cells. Early late stages were detected by Annexin V TUNEL methods, respectively. In parallel experiments, expression genes related apoptosis, BCL2, BCLXL, BAX, P53, APAF1, Caspase 3, 9, was determined RT-PCR. obtained data suggest that Dox/P85 formulation induces more efficiently than free Dox. treatment Dox alone simultaneously activated a proapoptotic signal antiapoptotic cellular defense. Therefore, induction substantially limited. contrast, significantly enhanced prevented activation likely result stronger response compared drug.
elsevier.com
sci-hub.se 参考文章(41)
Ricky W. Johnstone, Erika Cretney, Mark J. Smyth, P-Glycoprotein Protects Leukemia Cells Against Caspase-Dependent, but not Caspase-Independent, Cell Death Blood. ,vol. 93, pp. 1075- 1085 ,(1999) , 10.1182/BLOOD.V93.3.1075
L Campos, JP Rouault, O Sabido, P Oriol, N Roubi, C Vasselon, E Archimbaud, JP Magaud, D Guyotat, High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy Blood. ,vol. 81, pp. 3091- 3096 ,(1993) , 10.1182/BLOOD.V81.11.3091.3091
Patrice Xavier Petit, Naoufal Zamzami, Jean-Luc Vayssière, Bernard Mignotte, Guido Kroemer, Maria Castedo, Implication of mitochondria in apoptosis Molecular and Cellular Biochemistry. ,vol. 174, pp. 185- 188 ,(1997) , 10.1007/978-1-4615-6111-8_28
Annie Venne, Alexander Kabanov, Shengmin Li, Rosemonde Mandeville, Valery Alakhov, Hypersensitizing Effect of Pluronic L61 on Cytotoxic Activity, Transport, and Subcellular Distribution of Doxorubicin in Multiple Drug-resistant Cells Cancer Research. ,vol. 56, pp. 3626- 3629 ,(1996)
L Pylkkänen, S Toikkanen, H Joensuu, Bcl-2 protein expression and long-term survival in breast cancer. American Journal of Pathology. ,vol. 145, pp. 1191- 1198 ,(1994)
P Verderio, O Caffo, C Doglioni, P Bevilacqua, M Barbareschi, L Morelli, P Boracchi, G Gasparini, P D Palma, F A Mauri, Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. Clinical Cancer Research. ,vol. 1, pp. 189- 198 ,(1995)
Elena V. Batrakova, Valery Yu Alakhov, Donald W. Miller, Alexander V. Kabanov, Shu Li, Sergey V. Vinogradov, Mechanism of pluronic effect on P-glycoprotein efflux system in blood-brain barrier: contributions of energy depletion and membrane fluidization. Journal of Pharmacology and Experimental Therapeutics. ,vol. 299, pp. 483- 493 ,(2001)
E V Batrakova, S Li, W F Elmquist, D W Miller, V Y Alakhov, A V Kabanov, Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion. British Journal of Cancer. ,vol. 85, pp. 1987- 1997 ,(2001) , 10.1054/BJOC.2001.2165
T Minko, S.S Dharap, A.T Fabbricatore, Enhancing the efficacy of chemotherapeutic drugs by the suppression of antiapoptotic cellular defense. Cancer Detection and Prevention. ,vol. 27, pp. 193- 202 ,(2003) , 10.1016/S0361-090X(03)00067-9
Santos A. Susin, Naoufal Zamzami, Guido Kroemer, Mitochondria as regulators of apoptosis: doubt no more Biochimica et Biophysica Acta. ,vol. 1366, pp. 151- 165 ,(1998) , 10.1016/S0005-2728(98)00110-8