Korelasi Ekspresi X-Linked Inhibitor of Apoptosis Protein (XIAP) terhadap Resistensi Kemoterapi pada Model Kanker Payudara Tripel Negatif MDA-MB 231 secara in vitro

Abstract

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options and a high rate of chemotherapy resistance. Inhibition of apoptosis is a key mechanism contributing to treatment failure. X-linked inhibitor of apoptosis protein (XIAP) is a potent endogenous caspase inhibitor that suppresses programmed cell death and has been implicated in tumor progression and chemoresistance. This study aimed to evaluate the correlation between XIAP expression and chemotherapy resistance in an in vitro TNBC model. Methods: An experimental in vitro study was conducted using the TNBC MDA-MB-231 cell line. Cells were treated with paclitaxel and doxorubicin at various concentrations. Chemotherapy sensitivity was assessed using the MTT assay to determine cell viability and half-maximal inhibitory concentration (IC₅₀) values. XIAP expression levels were quantified using real-time polymerase chain reaction (RT-PCR). Statistical correlation analysis was performed to evaluate the relationship between XIAP expression and chemotherapy resistance. Results: Paclitaxel and doxorubicin induced a dose-dependent reduction in MDA-MB-231 cell viability. IC₅₀ analysis demonstrated reduced sensitivity of cells to both chemotherapeutic agents. XIAP expression was significantly increased in chemotherapy-resistant cell groups compared to controls. A significant positive correlation was observed between elevated XIAP expression and chemotherapy resistance (p < 0.05). Discussion: The findings indicate that increased XIAP expression is associated with reduced apoptotic response and enhanced chemotherapy resistance in TNBC cells. XIAP-mediated inhibition of caspase activation likely plays a central role in promoting tumor cell survival following chemotherapy exposure. These results support the potential of XIAP as a therapeutic target to overcome chemoresistance in triple-negative breast cancer.

Keywords: Triple-negative breast cancer; XIAP; chemotherapy resistance; apoptosis; MDA-MB-231