TABLE 3

Proposed molecular mechanisms involved in the additive-synergistic interaction of erlotinib and pemetrexed combination in NSCLC cells

Mechanism
Cell Lines
A549
SW1573
H460
H292
H1650
H1703
Increase of EGFR phosphorylation by pemetrexeda + ++ ++ + + ++
Induction of apoptosisb,c + + +/− ++ ++ +
Reduction of Akt phosphorylationa,c ++ ++ + + ++ +
Reduction of E2F-1 mRNA expressiona,c +/− ++ ++ ++ + +
Reduction of TS mRNA expressiona,c +/− + ++ + +/− +/−
Reduction of DHFR mRNA expressiona,c + + + + +/− +
Reduction of TS in situ activitya,c
+
++
++
++
++
++

  • ↵ a The modulation was classified as +/−, +, or ++ if the increase or reduction with respect to control values were <25%, between 25 and 50%, or >50%, respectively.

  • ↵ b The apoptosis induction was evaluated by AI values, as described under Materials and Methods, and was classified as +/−, +, or ++ if AI values were <10%, between 10 and 15%, or >15%, respectively.

  • ↵ c Cells were treated for 72 h to IC50 concentrations of the simultaneous erlotinib-pemetrexed combination.