PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells.

摘要: Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor prognosis owing to its resistance chemotherapy. RCC cells overexpress transcription factor, PAX2, normally expressed in fetal but downregulated at birth. Since Pax2 suppresses apoptosis during renal development, we reasoned that PAX2 may confer cisplatin-induced RCC. Here, show confers normal explants. Human embryonic 293 transfected with expression vector exposed cisplatin (40 μ M) exhibited 45±15% as much caspase-3 cleavage compared control cells. Conversely, murine collecting duct stably antisense cDNA had twofold increase apoptosis. Murine (embryonic day 15) explants from 1Neu +/- mice (25 M × 24 h) 50% increased (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining). We then (CAKI-1 (human, Caucasian, kidney, carcinoma) ACHN adenocarcinoma)) express protein. PAX2-small interfering RNA (100 nM) reduces endogenous protein (10% of baseline) induces (Annexin-V knockdown sensitized apoptosis, killing 50–60% cisplatin-resistant CAKI-1 These findings suggest non-transformed Similarly, overexpression contributes resistance. Conceivably, therapeutic strategy inactivates vivo might enhance efficacy conventional cytotoxic drugs against