Journal
DALTON TRANSACTIONS
Volume 51, Issue 13, Pages 5257-5270Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1dt03964d
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Funding
- National Natural Science Foundation of China [22077021]
- Natural Science Foundation of Guangxi [2017GXNSFEA198002]
- Guangxi Bagui Scholar Program
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By synthesising a series of novel platinum complexes, we discovered that C6 exhibits strong cytotoxicity against resistant lung cancer cells, inducing apoptosis and autophagy, and can reverse cisplatin-induced resistance.
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) in vitro and efficiently inhibited tumour growth in vivo. The Pt complexes can target DNA, lead to DNA platination and cause cell cycle arrest in the 5 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 via 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.
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