Endometrial cancer (EMCA) is a clinically heterogeneous disease. Previously, we tested the efficacy of Verteporfin (VP) in EMCA cells and observed cytotoxic and anti-proliferative effects. In this study, we analyzed RNA sequencing data to investigate the comprehensive transcriptomic landscape of VP treated Type 1 EMCA cell lines, including HEC-1-A and HEC-1-B. There were 549 genes with differential expression of two-fold or greater and P < 0.05 after false discovery rate correction for the HEC-1-B cell line. Positive regulation of TGFβ1 production, regulation of lipoprotein metabolic process, cell adhesion, endodermal cell differentiation, formation and development, and integrin mediated signaling pathway were among the significantly associated terms. A functional enrichment analysis of differentially expressed genes after VP treatment revealed extracellular matrix organization Gene Ontology as the most significant. CDC23 and BUB1B, two genes crucially involved in mitotic checkpoint progression, were found to be the pair with the best association from STRING among differentially expressed genes in VP treated HEC-1-B cells. Our in vivo results indicate that subcutaneous tumors in mice were regressed after VP treatment by inhibiting cell cycle pathway proteins. The present study revealed multiple key genes of pathological significance in EMCA, thereby improving our understanding of molecular profiles of EMCA cells.