KEAP1-dependent synthetic lethality induced by AKT and TXNRD1 inhibitors in lung cancer

pnrobinson commented 4 years ago

pnrobinson commented 4 years ago

MK2206:AKT inhibitor

Using cell proliferation assay and siRNA knockdown, we further validated the top 10 hits, including TXNRD1, CFLAR, ATP5J, SLC9A10, and CLN10. The results showed that knockdown of TXNRD1, CFLAR, SCLC9A10, AHCYL1, and CLN10 sensitized both HCC193 and H1993 cells to 1μM MK2206
We found that the expression levels of TXNRD1 are low in all 4 MK2206 sensitive cell lines, whereas the expressions of TXNRD1 are significantly higher in 7 out 10 resistant cell lines (P<0.01), and there is a correlation of TXNRD1 levels with MK2206 resistance
TXNRD1 knockdown sensitizes NSCLC cells to AKT inhibition by inducing cell apoptosis.

pnrobinson commented 4 years ago

done

monarch-initiative / SLDBGen