Pharmacological modulation of primary tumor growth and metastatic progression of Lewis lung carcinoma by directacting anticoagulants under cisplatin use

Abstract

Pharmacological modulation of tumor growth involves influencing various cellular and molecular pathways to inhibit tumor development or enhance the efficacy of anticancer therapy. This can be
achieved by targeting specific molecules involved in tumor cell growth, angiogenesis, or altering the tumor microenvironment and modulating the immune response to the tumor.
Anticoagulants in the context of cancer are used to prevent and treat thrombosis, which often occurs as a complication of the tumor process or anticancer therapy. These drugs are not directly antitumor
agents, but their use as accompanying drugs may expand the possibilities of antitumor therapy.
The aim of the study was to research the effect of direct-acting anticoagulants sulodexide and enoxaparin, in combination with the antitumor agent cisplatin, on the formation of metastases in the
lungs of male C57 BL/6 mice under a model of spontaneously metastatic Lewis lung carcinoma (LL) tumor growth; as well as to evaluate its effect on the platelet component of hemostasis, the coagulation activity of whole blood, and relationship with metastasis progression.
Before the inoculation of LL carcinoma cells, all experimental mice underwent blood clotting time analysis using the Morawitz method. The procedure was performed on days 14 and 28 of the study. On
day 28 of the study, the parameters of the primary tumor were assessed in the experimental animals. The animals were then euthanized, hematological parameters were measured, and the lungs were
harvested for metastasis count. According to the results of previous studies, the use of sulodexide and enocaparin as monotherapy allowed us to determine their effect on the metastatic activity of LL
carcinoma. We observed significant reduction in the metastatic activity of Lewis lung carcinoma when sulodexide was administered at a dose of 2 mg/kg in combination with cisplatin at a dose of 6 mg/kg.
According to data obtained, tumor progression was accompanied by disturbances in blood coagulation activity. The combined use of sulodexide and cisplatin significantly increased platelet count
and blood clotting time. Thus, a comparative analysis of these data revealed a significant reduction in the metastatic activity of Lewis lung carcinoma under the administration of the direct-acting anticoagulant sulodexide in combination with cisplatin. These findings may serve as a basis for the development of new therapeutic
strategies for cancer patients with malignancies characterized by hematogenous metastasis and targeted at platelet-related mechanisms.