The applications of cell growth kinetic model to the doxorubicin dose calculation for treatment of mammal gland cancer MCF-7
P.A. Gertsen Cancer Research Institute, Conservative Treatment Efficacy Prognosis Department, Russia, 1119234, Moscow, 2nd Botkinsky pass., 3. N.E. Bauman MSTU, Russia, 105005, Moscow, 2nd Baumanskaya str, 5.1 pp. (accepted)
For effective pharmacotherapy oncologic illnesses knowledge of the kinetics of the growth of neoplasm as in lack as in the presence of cytostatic agents, is imortant. For the description of population growth previously quazychemical (ecotoxicological) model based on the biology of cellcycle was proposed [Ershov, 1997]. The concordant equation of model has aspect:
t(C1) = ln( (C1/c0)((K1– C0)/(K1 – C1)) (1 + n) )/(n px ),
where t(С1) - time, through which is achieved the concentration of с1 cells directly following mitosis, C0 - the initial concentration of cells, K1 - saturated concentration of cells population following mitosis; n=K1/K2; K2=bx/a; px=р+g+d1; d1=d11X1; bx=b+d2; d2=d21X1; p, b, g, a, - kinetic coefficients characterizing growth processes, the ramifications (of breeding), naturally-occuring killing and autoinhibition untreated population chain; d11, d21 - the kinetic coefficients of the toxic effect of the cytostatic agent 1 (doxorubicin) comprised in media in concentrations K1, on the fraction of cells directly following mitosis and enterring into mitosis, accordingly. Catches eye the model application for the calculation of the internal-curative doses of antineoplastic and the plannings of the curing scheme.
To develop the technique of detecting of the internal-curative dose of doxorubicin on cell culture the mastoncus of man MCF-7 on basis quazychemical model of population growth.
The cultivation of the specimens of cells was conducted in laboratory 96-луночных plates in untreated media and in the doxorubicin presence in final concentrations 2.5 •10-4, 2.5 •10-3, 0.025, 0.25 and 2.5 мкг/мл during 7 сут. On 1, 2, 3, 7 days the number of cells in culture with applications of cytologic and spectrophotometric methods was assessed. Behind spectrophotometric method lay MTT - test. As to observation the kinetic curve dependences of the number of cells from time were built. By the method of the unlinear optimization of derived findings with the help of the bag of mathematical programs Mathсad® parameters of quazychemical model of growth were assessed. Entering number the last coefficients of the toxic effect of cytostatic agent served body for detecting of the minimal dose of doxorubicin augmenting cytocydic effect in cell culture.
The kinetics of the number of the man mastoncus of MCF-7 cells in culture in the presence of doxorubicin in the indicated concentrations is studied. Quazychemical model parameters are assessed. It is established that equation of model satisfactorily describes of cells number in culture ranging the error of experiment. Coefficients of d11 and d21 toxic effect are constant magnitudes, distinctive for this cytostatic agent. the internal-curative dose of doxorubicin fitting cytocydic concentrations for cell culture MCF-7 is assessed.
REFERENCES. Ershov Yu. A., The Theory of Chain Growth and Inhibition of Biological Populations by Chemical Agents. Dokl. Ross. Akad. Nauk, 1997, vol. 352, no. 5, p. 1.