Evaluation of the Anticancer Potential of Compound 107 via the VEGFA and VEGFR2 (KDR) Signaling Pathway in Colorectal Cancer: Integrative Analysis of Clinical, In Silico, and In Vitro Approaches

The VEGFA and VEGFR2/KDR signaling pathway is a major regulator of tumor angiogenesis and colorectal cancer (CRC) progression. This study investigated the anticancer effects of Compound 107 using integrated clinical, in vitro, and in silico approaches. VEGFA and KDR expression was evaluated in paired colorectal tumor and adjacent non-neoplastic tissues, while molecular docking and ADMET analyses were performed to characterize Compound 107. Its effects on viability, apoptosis, cell-cycle distribution, VEGFA/KDR gene expression, and VEGFA and VEGFR2 protein levels were assessed in HT-29 cells. VEGFA and KDR expression was significantly increased in CRC tissues by 1.98- and 2.02-fold, respectively (both p < 0.001), accompanied by increased protein immunoreactivity (both p < 0.0001). Compound 107 showed favorable predicted binding to VEGFA (−8.60 kcal/mol) and VEGFR2 (−8.30 kcal/mol), although ADMET analysis indicated limitations related to pharmacokinetic and toxicity profiles. Compound 107 reduced MTT-based metabolic viability in a concentration- and time-dependent manner, increased early apoptosis, decreased the G0/G1 population, and increased the S-phase population. Moreover, VEGFA and KDR gene expression and corresponding protein fluorescence intensities were significantly reduced following treatment. Collectively, Compound 107 reduced metabolic viability and increased early apoptosis, accompanied by reduced VEGFA and KDR expression in HT-29 cells. These findings indicate an association between the cellular effects of Compound 107 and changes in VEGFA/VEGFR2-related molecular markers; however, they do not demonstrate direct inhibition of the VEGFA/VEGFR2 signaling pathway. Further mechanistic studies are required to clarify this relationship.