Akademik Veri Yönetim Sistemi
2nd Eurosia Biochemical Approaches and Technologies Congress, Antalya, Türkiye, 26 - 29 Ekim 2019
In anti-cancer therapy, the effectiveness of
therapeutics is limited by mutations causing drug resistance.1KRAS mutations are the only
determinant for cetuximab resistance in colorectal cancer (CRC) patients.2Therefore,
it is very important to determine new predictive mutations in CRC treatment.3In this study,
the association of AKT1/CTNNB1 mutations with the drug resistance against cetuximab and some chemotherapeutics used
in the CRC treatment were investigated in vitro by using
site-directed mutagenesis, transfection, Western Blot methods, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
(MTS) cell growth inhibition assay. The cetuximab resistance was higher in the presence
of AKT1 E17K, E49K, and L52R mutations and, CTNNB1 T41A, S45F, and
S33P mutations compared to that of the WT. AKT1/CTNNB1 mutations were also determined to
be associated with oxaliplatin, irinotecan, SN-38, and 5-fluorouracil resistance.
Furthermore, mutant cell viability in oxaliplatin treatment was more effectively inhibited than that
of the other drugs. These findings provide evidence that CRC patients carrying AKT1/CTNNB1mutations may have resistance to cetuximab and frequently used chemotherapeutics,
and these mutations may serve as an
important predictive biomarker which responsible for drug resistance.