Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma.

Muhammad Shahidan Muhammad Sakri, Tengku Ahmad Damitri Al-Astani Tengku Din, Hasnan Jaafar, Vinod Gopalan, Wan Faiziah Wan Abdul Rahman

International journal of immunopathology and pharmacology 2022 Jan-Dec

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Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Citation

Muhammad Shahidan Muhammad Sakri, Tengku Ahmad Damitri Al-Astani Tengku Din, Hasnan Jaafar, Vinod Gopalan, Wan Faiziah Wan Abdul Rahman. Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma. International journal of immunopathology and pharmacology. 2022 Jan-Dec;36:20587384211059673