Figure 7.

Ovarian SKOV-3/CDDP cells develop resistance to cisplatin through various mechanisms, including oxidative stress, enhanced antioxidant thioredoxin (Trx/TrxR) system, and abnormal signaling pathways. QU pre-treatment has been shown to influence various targets, including Trx/TrxR anti-oxidant system and signaling pathways involved in tumor development and progression. This antioxidant system is composed of thioredoxin reductases (TrxR), thioredoxins (Trx-1), and nicotinamide adenine dinucleotide phosphate (NADPH). Reduced Trx is maintained by TrxR, which accept reducing equivalents from NADPH to the oxidized forms of Trx, that in turn catalyze the reduction of disulfides (s-s) within oxidized cellular proteins, such as (STAT3). Inhibition of TrxR by QU pre-treatment results in the accumulation of oxidized STAT3, which prevents STAT3-dependent transcription. QU pre-treatment also targets mTOR. Inhibition of mTOR is associated with inhibition of phosphorylation of STAT-3 at both Ser⁷²⁷ and Tyr⁷⁰⁵ that collectively inhibit SKOV-3/CDDP cell survival and proliferation.