Том 25, № 10 (2025)

Cancer, characterized by aberrant cell growth, presents a formidable health challenge, impacting millions of individuals worldwide each year. Among the myriad mechanisms facilitating tumor progression, Vascular Endothelial Growth Factor receptors (VEGFR) play a pivotal role in driving angiogenesis the process by which tumors develop their own blood supply. This vascularization not only supports tumor nourishment and growth but also facilitates metastasis, enabling cancer to spread to distant sites. VEGFR inhibitors offer a strategic approach to disrupt the VEGF-VEGFR binding pathway, thereby impeding angiogenesis, metastasis, and the proliferation of cancer cells. This review elucidates the latest advancements in medicinal chemistry pertaining to VEGFR inhibitors, showcasing a variety of chemical moieties and assessing their efficacy across different cancer cell lines. The novel compounds highlighted in this review exhibit significant promise for anticancer evaluation through targeted VEGFR kinase inhibition. A robust body of in vivo, in vitro, and ex vivo studies supports these findings, demonstrating the antitumor effects of these compounds. Computational analyses further enhance our understanding by predicting compound binding affinities, pharmacokinetics, and overall drug-likeness. Despite the significant progress made in developing effective VEGFR inhibitors, challenges remain in refining these agents for optimal cancer treatment. This review not only summarizes the advancements achieved in VEGFR inhibitor development but also emphasizes the ongoing hurdles that must be addressed to enhance the efficacy of cancer therapies.

Background:Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named Schisandra rubriflora (Franch.).

Purpose:In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 in vitro and in vivo.

Materials and Methods:In vitro, we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. In vivo, we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.

Results:We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 via JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, in vivo observation confirmed the antitumor activity of schisanhenol.

Conclusion:Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 via the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.

Introduction/Objective:Plants and their bioactive compounds play a crucial role in the pharmaceutical industry for treating cancer. To date, the cytotoxic and antiproliferative effects of Hypericum perforatum methanol extract on human thyroid cancer cell lines have not been thoroughly explored. The present study aimed to assess the potential anti-cancer effects of HPME on human thyroid cancer and investigate its potential therapeutic benefits.

Methods:HPME was prepared using the maceration method, and its antioxidant activity was examined. Cytotoxicity studies were then carried out, followed by an investigation of the possible effects of HPME on metastasis and colony-forming capacities of human thyroid cancer cells. Afterward, qRT-PCR, western blotting, and apoptosis assays were performed.

Results:Cytotoxicity studies revealed notable cytotoxicity of HPME against the TT cell line. Moreover, HPME significantly curtailed metastasis and invasion of TT cells in an in vitro wound healing assay. Analyses of gene expressions demonstrated an elevation in caspase-12, caspase-3, and Bax, coupled with a reduction in BcL-2, APOE, and CLU expression. Following HPME treatment, there was an increase in the protein expression levels of Bax and Caspase-12, while a decrease in the BcL-2, APOE, and CLU protein expression. Furthermore, apoptotic studies indicated an increase in early apoptosis.

Conclusion:Overall results revealed that HPME demonstrates a notable antioxidant capacity in human thyroid cancer. It exerts an influence on crucial biological processes associated with cancer, indicating its potential to hinder the proliferation of human thyroid cancer cells by enhancing apoptosis through the upregulation of gene and protein expression, particularly involving caspases.