JOURNAL OF BASIC AND CLINICAL HEALTH SCIENCES, no.1, pp.492-500, 2023 (ESCI)
Purpose: Abnormal Sonic Hedgehog signaling Pathway (Shh) activation is crucial for the development of cancer stem cells, neoplastic growth, and epithelial-mesenchymal transition processes in adulthood. Activation of the Hedgehog signaling pathway may induce the changes in cilia found in the cell membrane, initiates the Gli1 transcription factor that is translocated to the cell nucleus and finally, the target genes are transcribed. In this study, investigation of the antiproliferative, anti-invasive, and antimigrative effect of the combined use of robotnikinin (Ptch1 antagonist) and vismodegib (Smo inhibitor) on the hedgehog signaling pathway was aimed. Material and Methods: After demonstrating the presence of the hedgehog signaling pathway in the glioblastoma cell line U87-MG, the effect of the combined use of the robotnikinin and the vismodegib on the hedgehog signaling pathway was investigated. In-vitro cell proliferation, migration, and invasion analysis of the combination of antagonist and inhibitor and in silico drug-likeness analysis were performed. Results: Two different combinations of robotnikinin and vismodegib were tested. In vitro studies show that the combined use of agents in combined treatments of Smo and Ptch1 is more effective than their individual usage. Conclusion: Inhibition of the hedgehog signaling pathway with specific inhibitors and antagonists is considered an innovative strategy for cancer therapy.