Page 219 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology FN3K–Nrf2 axis inhibition in breast cancer

t-test or the Mann-Whitney U test, with adjustments for
multiple comparisons made through FDR correction.
3.3.1.1. FN3K expression analysis
The expression of FN3K was significantly downregulated
upon treatment with oxaliplatin, lansoprazole, and
capivasertib, with all three compounds showing highly
significant reductions (p<0.001; Figure 5). In contrast,
1-DMF exhibited a marginally significant reduction in
FN3K expression (p<0.05). Neither amiloride (p=0.092) nor
ritonavir (p=0.199) significantly altered FN3K expression
following FDR correction. These findings suggest that Figure 5. Treatment-specific expression of FN3K and Nrf2 genes
oxaliplatin, lansoprazole, and capivasertib act as effective in MCF-7 cells. The bar graph illustrates the fold change in
FN3K inhibitors, whereas amiloride and ritonavir do not FN3K and Nrf2 expression following treatment with oxaliplatin,
substantially influence FN3K levels in MCF-7 cells. lansoprazole, capivasertib, amiloride, ritonavir, and 1-DMF. Significant
downregulation of FN3K was observed with oxaliplatin, lansoprazole,
3.3.1.2. Nrf2 expression analysis and capivasertib (p<0.001), while Nrf2 expression was significantly
reduced by lansoprazole, amiloride, and ritonavir (p<0.001)
The expression of Nrf2 was significantly downregulated Abbreviations: 1-DMF: 1-deoxy-1-morpholino-D-fructose; FN3K:
by lansoprazole, amiloride, and ritonavir, with all three Fructosamine-3-kinase; Nrf2: Nuclear factor erythroid 2-related factor 2;
compounds demonstrating highly significant reductions ns: Not significant
(p<0.001; Figure 5). Oxaliplatin also suppressed Nrf2
expression but to a lesser extent, with statistical significance
at p<0.01. Meanwhile, 1-DMF exhibited a marginally
significant reduction (p<0.05). Capivasertib, however,
did not significantly alter Nrf2 expression (p=0.171).
Interestingly, although amiloride and ritonavir did not
significantly impact FN3K expression, both compounds
caused a pronounced suppression of Nrf2, suggesting a
potential alternative regulatory mechanism.

These results highlight that oxaliplatin, lansoprazole,
and capivasertib effectively inhibit FN3K, while
lansoprazole, amiloride, and ritonavir strongly suppress
Nrf2. The differential effects observed indicate that Figure 6. Treatment-specific expression of FN3K and Nrf2 genes in
while some compounds act directly on FN3K, others T-47D cells. FN3K and Nrf2 expression were significantly reduced in
may influence Nrf2 independently, warranting further response to oxaliplatin, lansoprazole, and capivasertib (p<0.001 for
FN3K; p<0.01 for Nrf2), suggesting a strong inhibitory effect
mechanistic exploration. Abbreviations: FN3K: Fructosamine-3-kinase; Nrf2: Nuclear factor
erythroid 2-related factor 2
3.3.2. Differential expression of FN3K and Nrf2 in
T-47D Cells This consistent suppression of Nrf2 suggests that these

3.3.2.1. FN3K expression analysis compounds may exert a dual effect by not only inhibiting
The expression of FN3K was significantly downregulated FN3K but also reducing Nrf2 levels in T-47D cells. The
by oxaliplatin, lansoprazole, and capivasertib, with all concurrent inhibition of both FN3K and Nrf2 may enhance
three treatments displaying highly significant reductions the therapeutic relevance of these compounds by targeting
(p<0.001; Figure 6). This strong statistical significance key regulatory pathways involved in cancer progression.
indicates that these compounds may act as potent FN3K
inhibitors in T-47D cells, reinforcing their inhibitory 3.3.3. Differential expression of FN3K and Nrf2 in
effects observed in other breast cancer cell models. BT-474 Cells
3.3.2.2. Nrf2 expression analysis 3.3.3.1. FN3K expression analysis
Oxaliplatin, lansoprazole, and capivasertib all significantly The expression of FN3K was significantly downregulated
downregulated Nrf2 expression, with p-values falling by oxaliplatin, lansoprazole, and capivasertib, with all
below the 0.01 threshold after FDR correction (Figure 6). three treatments displaying highly significant reductions

Volume 9 Issue 3 (2025) 211 doi: 10.36922/EJMO025150114