Bioinformatics and In Vitro Evaluation of The Potential of Cucurbitacin E as a Chemosensitizer in MCF-7/HER2 Cells
Inas Haidar, Dr. apt. Dyaningtyas Dewi Pamungkas Putri, M.Sc.; Prof. Dr. rer. nat. apt. Adam Hermawan, S.farm M.Sc.
2026 | Tesis | S2 Ilmu Farmasi
Background: Globally, breast cancer continues to be a primary contributor to oncology-related mortality. In particular, HER2-positive subtypes present major clinical challenges, as they are frequently linked to unfavorable clinical outcomes and resistance to conventional therapies.
Objective: This study aimed to investigate the chemosensitizer potential of Cucurbitacin E in MCF-7/HER2 cells through integrated bioinformatics and in vitro approaches.
Methods: Potential molecular targets of CuE associated with lapatinib resistance were identified using bioinformatics analysis involving gene target prediction, protein-protein interaction (PPI), enrichment analysis, and hub gene identification. Further in vitro validation was conducted in MCF-7/HER2 cells involving MTT assay, colony forming assay, and quantitative real time PCR (qRT-PCR).
Results: Bioinformatics analysis identified ten hub genes associated with resistance-related signaling networks. In vitro studies identified IC50 values of 1.73 µM and 17.07 µM for CuE and lapatinib respectively. Subsequent combination assay showed enhanced lapatinib sensitivity using lower concentrations, it is also shown that the combination could reduce the colony forming ability of MCF-7/HER2 cells. Gene expression analysis showed significantly reduced AKT1expression following combination treatment, and the presence of adaptive compensatory transcriptional responses including the ESR1, EGFR, and STAT3.
Conclusions: Cucurbitacin E displays chemosensitizer potential in combination with lapatinib on the MCF-7/HER2 cells. The combination of CuE and lapatinib inhibited cell viability, suppressed long term proliferation, and modulated key resistance-related genes. These results support further investigation of CuE as a complementary strategy to overcome lapatinib resistance cells.
Background: Globally, breast cancer continues to be a primary contributor to oncology-related mortality. In particular, HER2-positive subtypes present major clinical challenges, as they are frequently linked to unfavorable clinical outcomes and resistance to conventional therapies.
Objective: This study aimed to investigate the chemosensitizer potential of Cucurbitacin E in MCF-7/HER2 cells through integrated bioinformatics and in vitro approaches.
Methods: Potential molecular targets of CuE associated with lapatinib resistance were identified using bioinformatics analysis involving gene target prediction, protein-protein interaction (PPI), enrichment analysis, and hub gene identification. Further in vitro validation was conducted in MCF-7/HER2 cells involving MTT assay, colony forming assay, and quantitative real time PCR (qRT-PCR).
Results: Bioinformatics analysis identified ten hub genes associated with resistance-related signaling networks. In vitro studies identified IC50 values of 1.73 µM and 17.07 µM for CuE and lapatinib respectively. Subsequent combination assay showed enhanced lapatinib sensitivity using lower concentrations, it is also shown that the combination could reduce the colony forming ability of MCF-7/HER2 cells. Gene expression analysis showed significantly reduced AKT1expression following combination treatment, and the presence of adaptive compensatory transcriptional responses including the ESR1, EGFR, and STAT3.
Conclusions: Cucurbitacin E displays chemosensitizer potential in combination with lapatinib on the MCF-7/HER2 cells. The combination of CuE and lapatinib inhibited cell viability, suppressed long term proliferation, and modulated key resistance-related genes. These results support further investigation of CuE as a complementary strategy to overcome lapatinib resistance cells.
Kata Kunci : Combinatorial strategies, HER2-positive breast cancer, PI3K/AKT signaling
