The best characterized kinase phosphorylating AKT S473 is mTORC2, a protein complex made up of mTOR, mLST8, and Rictor. We conducted siRNA for the Rictor subunit of mTORC2 and show that Icotinib 610798-31-7 knockdown had no significant impact on platinum response. Moreover, Rictor knockdown has no impact on platinum mediated phosphorylation of AKT S473 in resistant SKOV3 cells. Rapamycin treatment also fails to prevent cisplatin mediated induction of pAKT S473 and really appears to inhibit the apoptotic response to cisplatin. Eventually, IP in the absence and presence of jewelry failed to reveal any relationship between AKT and Rictor. We conclude that mTORC2 isn’t involved in cisplatin mediated activation of AKT and that mTOR in general might be not involved in the downstream prosurvival aftereffects of activated AKT in platinum resistant cells. DNA PK Phosphorylates AKT S473 in Response to Cisplatin in the Nucleus of Platinum Resistant, But Not Sensitive, Cells and Enhances Cisplatin Response in Clinically Resistant Cells Gene expression without Affecting Insulin Mediated AKT Activation We next deemed if DNA PK was responsible for platinummediated prosurvival activation of AKT seen on order of clinical platinum resistance in ovarian cancer. Relationship between AKT and DNA PK was detected by Internet Protocol Address in platinum resistant cells. By contrast, this interaction was often maybe not seen or was less readily detectable in intrapatient matched painful and sensitive cells. Knock-down of DNA PKcs somewhat increased apoptotic response to cisplatin in PEO4, SKOV3, PEA2, and PEO23 resistant ovarian cancer cells. Western blot analysis showed that, in the absence of DNA PKcs, platinum induced activation of AKT by phosphorylation at S473 was ablated. Phosphorylation of AKT at T308, known to be catalyzed by PDK1, was untouched by DNA PKcs Fostamatinib molecular weight knock-down confirming site specific activity and showing that T308 phosphorylation alone is insufficient for the platinum resistant phenotype. Provided platinums mode of damaging DNA, action, and the function of DNA PK in DNA repair, we performed immunofluorescent confocal microscopy, which revealed nuclear accumulation of pAKT in immune cells within 30-minutes of jewelry treatment with apparent cytoplasmic re-distribution by 8 hours. By comparison, jewelry sensitive cells do not acquire nuclear pAKT. Nuclear pAKT was established by subcellular fractionation studies, which also indicated mitochondrial redistribution of pAKT at 8 hours. Together with the IP and siRNA data, this suggests AKT is activated in the nucleus by DNA PKcs after cisplatin induced DNA damage in platinumresistant, although not platinum sensitive, cells and subsequently redistributes to mitochondria. Next we considered the broader effects of these preliminary observations utilizing the DNA PK inhibitor, NU7026.