Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines.

作者: Mayra L. Sottile , Antonella D. Losinno , Mariel A. Fanelli , F. Darío Cuello-Carrión , M. Magdalena Montt-Guevara

DOI: 10.3109/02656736.2015.1026848

关键词: Flow cytometryDNA repairImmunofluorescenceBiologyDNA mismatch repairMSH2CisplatinHyperthermiaHeat shock proteinMolecular biology

摘要: AbstractPurpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events the synthesis heat shock proteins (HSPs), which are able associate components from DNA repair mechanisms. However, little known about relationship mismatch system (MMR). Our aim was study effects hyperthermia on cisplatin (cPt) sensitivity and determine whether MLH1 MSH2 Hsp27 Hsp72 MMR-deficient(−)/-proficient(+) cells.Materials methods: HCT116+ch2 (MMR−) HCT116+ch3 (MMR+) cell lines were exposed cPt or without previous (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting flow cytometry performed.Results: increased resistance MMR− cells 1.42-fold. Immunofluorescence revealed that after cPt, translocated nucleus colocalisation coefficients b...

参考文章(56)
Andre Fedier, Daniel Fink, Angela Stuedli, Presence of MLH1 protein aggravates the potential of the HSP90 inhibitor radicicol to sensitize tumor cells to cisplatin. International Journal of Oncology. ,vol. 27, pp. 1697- 1705 ,(2005) , 10.3892/IJO.27.6.1697
Gloria C. Li, Kent E. Wallner, Effect of drug exposure duration and sequencing on hyperthermic potentiation of mitomycin-C and cisplatin. Cancer Research. ,vol. 47, pp. 493- 495 ,(1987)
A P Arrigo, J P Suhan, W J Welch, Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein. Molecular and Cellular Biology. ,vol. 8, pp. 5059- 5071 ,(1988) , 10.1128/MCB.8.12.5059
Sibylle Nebel, Randolph D. Christen, Stefan Aebi, Stephen B. Howell, Hua Zheng, Bruno Cenni, Alissar Nehmé, Daniel Fink, The role of DNA mismatch repair in platinum drug resistance. Cancer Research. ,vol. 56, pp. 4881- 4886 ,(1996)
Kenzo Ohtsuka, Andrei Laszlo, The relationship between hsp 70 localization and heat resistance Experimental Cell Research. ,vol. 202, pp. 507- 518 ,(1992) , 10.1016/0014-4827(92)90106-I
Joseph L. Roti Roti, Heat-induced alterations of nuclear protein associations and their effects on DNA repair and replication. International Journal of Hyperthermia. ,vol. 23, pp. 3- 15 ,(2007) , 10.1080/02656730601091759
K. Ohnishi, T. Ohnishi, Heat-induced p53-dependent signal transduction and its role in hyperthermic cancer therapy. International Journal of Hyperthermia. ,vol. 17, pp. 415- 427 ,(2001) , 10.1080/02656730110063604
Dong Wang, Stephen J. Lippard, Cellular processing of platinum anticancer drugs. Nature Reviews Drug Discovery. ,vol. 4, pp. 307- 320 ,(2005) , 10.1038/NRD1691
J. R. Lepock, Role of nuclear protein denaturation and aggregation in thermal radiosensitization. International Journal of Hyperthermia. ,vol. 20, pp. 115- 130 ,(2004) , 10.1080/02656730310001637334
David M. Guttmann, Lori Hart, Kevin Du, Andrew Seletsky, Constantinos Koumenis, Inhibition of Hsp27 radiosensitizes head-and-neck cancer by modulating deoxyribonucleic acid repair. International Journal of Radiation Oncology Biology Physics. ,vol. 87, pp. 168- 175 ,(2013) , 10.1016/J.IJROBP.2013.05.028