Investigation of Mechanism Activity of Antitumor and Radiosensitizing Activity of Preparations К-26 and K-26w
American Journal of Biomedical and Life Sciences
Volume 8, Issue 5, October 2020, Pages: 131-136
Received: Jul. 11, 2020;
Accepted: Jul. 28, 2020;
Published: Sep. 7, 2020
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Adil Ahmedovich Ibragimov, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Zulfiya Mahmudovna Enikeeva, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Nigora Alimuhamedovna Agzamova, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Faizullo Saifyllaevich Salihov, The Bukhara Oncological Centre, Bukhara, Uzbekistan
Okiljon Abduhalilovich Rahimov, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Mavluda Turapovna Askarova, Department of Macroeconomic Analysis and Forecasting, Tashkent State Economic University, Tashkent, Uzbekistan
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Introduction. Tropolone alkaloid – colchicine, there is very interesting object for synthesis of its derivatives, with such properties as, alkylation, a low toxicity, high antineoplastic activity and especially overcoming of multidrug resistance (MDR). We had been developed the antineoplastic preparation К-26 derivative of colchicine. К-26 has shown high cytotoxic activity on 60 lines of tumoral cells of the human in vitro, at National Institute of the Cancer of the USA (NCI). Further on the basis of К-26 its water-soluble form named term К-26w has been received. The work purpose. Studying of the mechanism of action of preparations К-26 and К-26w on: alkylating ability, mitotic activity, topoisomerase II, MDR2, р53 and colony-forming cells spleen (CFCs). Materials and methods. All researches have been carrying out by a standard technique. Studying mitotic activity of preparations was carrying out on duodenum and tumor СаРа after preparation influence. On models of a tumor of the Sarcoma 180 action of preparations has been investigated: the alkylating - on synthesis DNA/RNA, nucleosoma DNA degradation, activity topoisomerase II; on an expression MDR2 and р53 genes. Studying CFCs carry out by a standard technique on outbred mice. Results. К-26, К-26w and etoposide inhibited in cells of the Sarcoma 180: synthesis DNA/RNA on 84/65%, 95/85% and 55/35%, accordingly, in relation to the control; activity topoisomerase II on 80%, 90% and 60% accordingly. By method RT-PCR it is shown, К-26, К-26w and etoposide: inhibited an expression of MDR2 gene on 83%, 91% and 62%; increase expression р53 gene to 74%, 88% and 55%, accordingly, under the relation of the control of referential gene GARDH (100%). High ability К-26 and К-26w in an induction apoptosis tumoral cells and CFCs to 12 units is shown. Conclusion. Revealed ability К-26 and К-26w to suppress synthesis DNA/RNA activity topoisomerases, to stimulate р53, and also to suppress an expression of a multidrug resistance MDR2 gene, it explains their high antineoplastic activity which is connected with mitotic activity leading to cell fission synchronization, and radiosensitization activity. Special interest represents found at К-26w and К-26 suppression MDR2 as they are aimed for treatment of such resistant tumor as a kidney cancer. Stimulation CFCs which provides formation of haemopoetic and immune cells can protect an organism from their intensive cytotoxic action.
К-26, K-26w, Sarcoma 180, Topoisomerase II, MDR2, p53, CFCs
To cite this article
Adil Ahmedovich Ibragimov,
Zulfiya Mahmudovna Enikeeva,
Nigora Alimuhamedovna Agzamova,
Faizullo Saifyllaevich Salihov,
Okiljon Abduhalilovich Rahimov,
Mavluda Turapovna Askarova,
Investigation of Mechanism Activity of Antitumor and Radiosensitizing Activity of Preparations К-26 and K-26w, American Journal of Biomedical and Life Sciences.
Vol. 8, No. 5,
2020, pp. 131-136.
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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