Figure 5.

The killing of osimertinib-resistant NSCLC cells requires [BAX + BAK] and autophagosome formation and is significantly reduced by expression of activated AKT, activated mTOR or activated MEK1. Afatinib-resistant and osimertinib-resistant H1975 cells were transfected with siRNA molecules to knock down protein expression or with plasmids to express regulatory proteins. Subsequently, cells were treated with vehicle or [pemetrexed (500 nM) + GZ17-6.02 (2 μM curcumin final)] in combination for 24 h. Cell viability was determined by trypan blue exclusion (n = 3 ± SD). *p < 0.05 less than corresponding siSCR/CMV value; **p < 0.05 less than the corresponding values in afatinib-resistant cells; ^¶ p < 0.05 less than the corresponding values in all other conditions; ^§ p < 0.05 greater than the corresponding values in all other manipulated conditions.