Design of a novel Pt(II) complex to reverse cisplatin-induced resistance in lung cancer a multi-mechanism.

In order to develop a novel platinum (Pt) complex aiming to overcome cisplatin resistance, we synthesised a series of novel Pt complexes (C1-C6). These Pt complexes displayed potent cytotoxicity activity against resistant lung cancer cells (A549cisR) and efficiently inhibited tumour growth . The Pt complexes can target DNA, lead to DNA platination and cause cell cycle arrest in the S phase, thus impeding precise DNA synthesis. C6, in particular, induced not only apoptosis but also lethal autophagy in A549cisR cells. In addition, these novel Pt complexes reversed cisplatin-induced resistance inhibiting the expression of P-glycoprotein and decreasing the level of glutathione in A549cisR cells. Moreover, the ERK pathway was involved in C6-induced overcoming cisplatin resistance.