Drug Res (Stuttg) 2020; 70(02/03): 86-90
DOI: 10.1055/a-0824-6325
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Efficacy of Gemcitabine on Intracranial Erlich Tumor and its Determinants

Alexander N. Stukov
1  Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
,
Vladimir G. Bespalov
2  Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
4  International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
,
Valerij A. Alexandrov
2  Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
4  International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
,
Alexander L. Semenov
2  Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
4  International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
,
Galina S. Kireeva
3  Laboratory of Carcinogenesis and Aging, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
,
Tatjana Y. Semiglazova
1  Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
,
Larisa V. Filatova
1  Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia
,
Denis A. Baranenko
4  International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
› Author Affiliations
Acknowledgement This study was partially funded by Government of Russian Federation, Grant RFMEFI58117X0020.
Further Information

Publication History

received 16 July 2018

accepted 13 December 2018

Publication Date:
25 September 2019 (online)

Abstract

Gemcitabine is quite effective in the treatment of brain tumors, although this drug has a limited ability to overcome the blood-brain barrier (BBB). Aim of study is to assess the therapeutic efficacy of gemcitabine and other drugs with different permeability of BBB in the model of intracranial tumor. The therapeutic activity of gemcitabine, carmustine, cyclophosphamide and cisplatin was studied in mice with intracranially implanted Ehrlich tumor, and also gemcitabine in various doses - with intramuscularly implanted tumor. On intracranial tumor model gemcitabine (25 mg/kg) increased the life span (ILS) by 60−89% (p<0.001), despite the fact that its permeability of the BBB is about 10%. Therapeutic activity of carmustine, cyclophosphamide and cisplatin (ILS were 44, 22 and 11%, respectively) corresponds with the BBB permeability for these drugs (90, 20 and 8%, respectively). On intramuscular tumor model, gemcitabine showed significant antitumor effect at both 25 and 2.5 mg/kg, indicating a wide range of therapeutic doses of this drug. Pronounced therapeutic effect of gemcitabine on intracranial tumor most likely is due to the small but sufficient concentration of the drug that overcomes the BBB.