Effects of adjuvant propofol on antitumoral effects of carboplatin in experimental endometrial cancer: possible epigenetic associations.

Endometrial cancer (EC) is a gynecological malignancy classified into two biologically distinct subtypes, Type I and Type II EC. The more aggressive Type II EC exhibits a poor response to conventional platinum-based chemotherapy. Propofol, an anesthetic agent in gynecologic surgery, has been reported to exert antitumor effects beyond anesthesia; however, its role as a chemoadjuvant in EC remains insufficiently explored. In this study, we investigated the effects of propofol combined with carboplatin on drug resistance- and metastasis-associated microRNAs and genes using in vitro and in vivo Type II EC model. Propofol treatment significantly reduced cancer cell viability and migratory capacity, while the combination treatment showed greater antimetastatic effects compared with carboplatin alone. In xenograft models, combination therapy resulted in a significant reduction in tumor volume and suggested reduced metastatic involvement in lung and liver tissues. Molecular analyses revealed downregulation of oncogenic microRNAs (miR-21, miR-135a) and upregulation of tumor-suppressive microRNAs (miR-34b, miR-98), accompanied by reduced mTOR, c-Myc, MRP7, and N-cadherin expression and increased PTEN and HMGB1 levels. Collectively, these findings indicate that propofol is associated with greater antitumor effects when combined with carboplatin, accompanied by changes in miRNA-gene expression patterns.