Evaluation of the antitumor efficacy of doxorubicin in monotherapy and in combination with a hif-1α inhibitor in a vivo model of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent form of primary liver cancer, ranking among the most common and lethal forms of oncological diseases. Transarterial chemoembolization (TACE) is one of the standard treatments for unresectable HCC, in which one of the key points is the embolization of tumor arteries, resulting in hypoxia that activates the HIF-1α signaling pathway. According to numerous literary data, bortezomib (BTZ) is capable of blocking the biological effects of HIF-1α. Based on the analyzed data, it can be assumed that the combination of bortezomib and TACE may lead to a synergistic effect, increasing the effectiveness of therapy and improving the prognosis for patients with unresectable HCC. In our work, we attempted to improve the antitumor efficacy of doxorubicin by combining it with an HIF-1α inhibitor in a model of hepatocellular carcinoma. During this study, it was established that the most effective suppression of tumor growth occurred in group 3, in animals with reduced blood flow and the administration of doxorubicin. The mean volume of tumor nodules was 395.33±95.70 mm3 (p<0.05), which was 2.1 times smaller than the mean volume in the control group, which was 830.56±144.86 mm3. In Group 2, in animals with reduced blood flow and the use of a combination of doxorubicin and bortezomib, the mean tumor node volume was 761.48 ± 117.95 mm³, which did not differ statistically from the volume of tumor nodes in the control group. Our findings indicate that a reduction in hepatic vascular blood flow in conjunction with doxorubicin exerts a pronounced inhibitory impact on the proliferation of intrahepatic tumor nodes. However, the introduction of bortezomib to this regimen does not result in the inhibition of tumor growth. Nevertheless, our results provide a rationale for a more comprehensive investigation of the mechanisms underlying the antitumor response or the reasons for its absence, as well as alternative candidates for HCC therapy. Keywords: liver cancer, hepatocellular carcinoma, bortezomib, HIF-1α, TACE, HepG2.