Poster Presenter

Phenomenological Model Of The Emergence Of Cancer Cell Resistance To Chemotherapy
Galina Dovbeshko, Galina Solyanik
Ukraine

It is known that drug resistance is one of the factors resulting to failure of a treatment of the number of diseases (inflammation, oncology, pediatrics, etc.). In spite of a great number of investigations the mechanisms of the emergence of drug resistance are still unknown. As tumor progression is based on genetic instability, the main targets of antineoplastic drugs are cell membrane and DNA. Our previous experiments [1-2]. showed the drastic differences between structure of DNA and phospholipids extracted from cisplatin-sensitive and cisplatin-resistant (as well as doxorubicin-sensitive and doxorubicin –resistant) variants of Guirin carcinoma strains. Moreover the treatment of rats with sensitive or resistant tumors by doxorubicin or cisplatin resulted in considerable changes in structural components of the cells. The SEIRA ( surface enhanced infrared) spectroscopy data of nucleic acids from sensitive- and drug-resistant rat tumours showed that DNA from resistant cells could be characterized as rigid structure and not changed after drug application. The structure of DNA from sensitive strain cells is flexible and application of anti-cancer drugs causes to numerous changes in its structure. The molecular structure of phospholipids from resistant and sensitive strains after application of anti-cancer drugs is modified also. On the basis of the experimental data we propose a model of interaction of the anticancer drug with the cancer cell components, mainly, DNA and membrane. The model include a): the drug interaction with target, b) target modification, c) modification of the drug during the process of incoming in membrane and under interactions with different cell component.The model could be applied in pharmacology and has importance for basic knowledge.

1. Chekhun V. F., Solyanik G. I., Kulik G.I., Tryndiak V.P., Todor I.N., Dovbeshko G.I., Repnytska O.P. Journal of Experimental Clinical Cancer Research. – 2002. – Vol.21, No4. – P.599-607

2. Structural organisation of nucleic acids from tumour cells / Repnytska O.P., Dovbeshko G.I., Tryndiak V.P., Todor I.M. and Kosenkov D.V. Faraday Discuss. – 2004. – Vol.126. – P.61 – 76.