Propofol Potentiates the Antitumor Efficacy of Carboplatin in Type II Endometrial Carcinoma through Epigenetic Regulation of Drug Resistance and Metastasis-Associated Genes and microRNAs

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 by 28% and migratory capacity by 34% (p < 0.01), while combination treatment enhanced antimetastatic effects compared with carboplatin alone. In xenograft models, combination therapy resulted in a 42% reduction in tumor volume (p < 0.001) and markedly decreased lung and liver metastasis. Molecular analyses revealed downregulation of oncogenic microRNAs (miR-21, miR-135a, miR-449) 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 enhances carboplatin antitumor efficacy through epigenetic modulation of microRNA–gene networks and may represent an adjuvant strategy in Type II EC.