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

cancer subtypes, qPCR analysis was further performed on These findings further reinforce the consistency of
T-47D and BT-474 cell lines. Vero cells were incorporated FN3K inhibition across multiple breast cancer cell lines.
as a non-malignant control model to evaluate the selectivity Lansoprazole consistently exhibited the highest FN3K
of the tested compounds toward malignant cells. suppression across MCF-7, T-47D, and BT-474 models,
with inhibition levels ranging from 99.98% to 99.99%.
3.2.2.2. FN3K and Nrf2 expression in T-47D Cells Similarly, oxaliplatin and capivasertib maintained robust
The impact of oxaliplatin, lansoprazole, and capivasertib and reproducible FN3K inhibition across all cell lines,
on the expression of FN3K and Nrf2 was assessed in T-47D with suppression levels ranging from 99.6% to 99.99%. The
cells, demonstrating a consistent downregulation of FN3K, consistency of these results across various breast cancer
comparable to the pattern observed in MCF-7 cells. In subtypes – including ER-positive, HER2-positive, and
the untreated control group, baseline expression levels triple-negative models – indicates the broad-spectrum
were recorded as 1.010 for FN3K and 1.060 for Nrf2. potential of these compounds as FN3K inhibitors, thereby
Among the tested compounds, lansoprazole displayed the reinforcing their prospective therapeutic value in various
highest degree of FN3K inhibition, reducing expression breast cancer settings.
by 99.99% (1.00 × 10 ), along with significant suppression
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of Nrf2 (0.029, ↓97.2%). Oxaliplatin also exhibited 3.2.2.4. FN3K and Nrf2 expression in Vero cells
potent FN3K downregulation (↓99.6%), reducing FN3K The expression patterns of FN3K and Nrf2 in Vero cells were
expression to 0.004, with corresponding Nrf2 suppression assessed following treatment with oxaliplatin, lansoprazole,
of 0.028 (↓97.3%). Similarly, capivasertib strongly inhibited and capivasertib. In contrast to the strong inhibitory effects
FN3K expression (↓99.97%), reducing it to 2.60 × 10 , with observed in breast cancer cell lines, these compounds
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a moderate suppression of Nrf2 (0.056, ↓94.7%). exhibited minimal to no suppression of FN3K in Vero
cells. In the untreated control group, baseline expression
These results indicate that FN3K suppression by
lansoprazole, oxaliplatin, and capivasertib in T-47D cells levels of FN3K and Nrf2 were 1.040 and 1.000, respectively.
is consistent with trends observed in MCF-7 cells. Notably, Oxaliplatin resulted in a modest 12% reduction in FN3K
lansoprazole demonstrated the highest FN3K inhibition expression, lowering it to 0.880, while Nrf2 remained
in T-47D (↓99.99%), exceeding its effect in MCF-7 cells, unchanged at 1.010, indicating no significant impact on this
further reinforcing its potential as a potent FN3K inhibitor. pathway. Lansoprazole caused a slight FN3K suppression of
Similarly, oxaliplatin and capivasertib maintained 9%, reducing expression to 0.910, and also mildly inhibited
strong FN3K suppression across both cell lines (↓99.6 Nrf2 to 0.890, representing an 11% decrease. Capivasertib
did not alter FN3K expression, which remained at 1.010,
– 99.99%), confirming their effectiveness in targeting and induced only a minor suppression in Nrf2 to 0.950,
FN3K-dependent pathways. These findings suggest that representing a 5% decrease.
FN3K inhibition by these compounds is not restricted to
a specific cell line but represents a consistent biological These results suggest that FN3K inhibition by oxaliplatin,
response, further validating their therapeutic relevance. lansoprazole, and capivasertib is not prominent in non-
malignant Vero cells, in stark contrast to their effects in
3.2.2.3. FN3K and Nrf2 expression in BT-474 Cells breast cancer models. The lack of substantial FN3K
The expression patterns of FN3K and Nrf2 were analyzed suppression in Vero cells indicates a degree of specificity
in BT-474 cells following treatment with oxaliplatin, toward malignant cells, as observed in MCF-7, T-47D,
lansoprazole, and capivasertib, revealing strong and and BT-474. Furthermore, the minimal changes in Nrf2
consistent downregulation of FN3K across all tested expression across treatments further support the idea that
conditions. In the untreated control group, baseline these compounds may exert selective effects depending
expression levels of FN3K and Nrf2 were 1.020 and 1.050, on the cellular context. These observations underscore
respectively. Lansoprazole demonstrated the most potent the differential regulatory effects of the tested compounds
FN3K inhibition, reducing its expression by 99.98% on FN3K and Nrf2 expression in cancerous versus non-
to 0.000, while also significantly suppressing Nrf2 to cancerous cell lines, supporting their therapeutic potential
0.060, representing a 94.3% reduction. Oxaliplatin also in cancer management while indicating a comparatively
showed strong FN3K suppression, reducing expression minimal impact on normal cells.
by 99.7% to 0.003, with Nrf2 downregulated to 0.104,
corresponding to a 90.1% decrease. Similarly, capivasertib 3.2.3. Comparative analysis of FN3K and Nrf2
exhibited substantial FN3K inhibition of 99.88%, lowering downregulation: Cancer vs. normal cells
expression to 0.001, and moderately suppressing Nrf2 to qPCR was employed to investigate the expression patterns
0.067, representing a 93.5% reduction. of FN3K and Nrf2 in three human breast cancer cell lines

Volume 9 Issue 3 (2025) 209 doi: 10.36922/EJMO025150114