In vitro study reveals selective cytotoxicity of a homogeneous trastuzumab-triptolide conjugate in HER2-overexpressing ovarian cancer cells, indicating potential for targeted therapy.
Key Points
To develop a stable and homogeneous antibody-drug conjugate by linking triptolide to trastuzumab via a bifunctional dibromomaleimide linker for targeted treatment of HER2-overexpressing ovarian cancer.
Synthesized a bifunctional dibromomaleimide (DBM) linker from 3,4-dibromofuran-2,5-dione to attach triptolide to trastuzumab through site-specific antibody cysteine disulfide rebridging.
Evaluated cytotoxic potency, apoptosis induction, cell cycle arrest, and HER2 receptor modulation in high-HER2 (SKOV-3) versus low-HER2 (OVCAR-8) ovarian cancer cell lines using flow cytometry.
The homogeneous conjugate demonstrated enhanced cytotoxic potency with lower IC50 values in HER2-high SKOV-3 cells compared to HER2-low OVCAR-8 cells.
Conjugate treatment caused concentration-dependent increases in Caspase-3/7 activation, substantial cell cycle arrest, and significant downregulation of HER2 surface levels in SKOV-3 cells.