ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta Т. 17, No. 2 , 2024
P. 64-66, Bibliography 5, Engl.
UDC:: 577:616
DOI: https://doi.org/10.15407/biotech17.02.064:
SYNERGISTIC ANTI-TUMOUR EFFECT OF DOXORUBICIN-HYDROCHLORIDE WITH CRM197, AN INHIBITOR OF HB-EGF, IN SQUAMOUS-CELL CARCINOMA
I.I. RADEVYCH 1,2, A.A. SIROMOLOT 2,3, D.V. KOLYBO 2
1 Educational Scientific Institute of High Technologies of Taras Shevchenko National University of Kyiv;
2 Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv;
3 ESC «Institute of Biology and Medicine» of Taras Shevchenko National University of Kyiv.
Recent studies have shown that cross-reacting material (CRM197), a nontoxic variant of diphtheria toxin, may may be necessary in treating cancers with poor prognoses. Doxorubicin-hydrochloride (DOX) is an antineoplastic prescription medicine for the treatment of certain types of cancer. CRM197 is a known carrier in targeted delivery, so CRM197-DOX complexes might be a step toward targeted therapy and reducing overall toxicity.
Aim. This study aims to explore the potential to inhibit the growth of tumour cells. To achieve that goal, we evaluated the usage of CRM197-DOX complexes in squamous carcinoma cell line A431 and compared it with the effect on other immortalised cell lines.
The methods used in this research include derivation and purification of recombinant CRM197 through immobilized-metal affinity chromatography and electrophoresis in a denaturing polyacrylamide gel. DOX-loaded CRM197 complexes were formed by adding a 5 μM doxorubicin solution to 0.5 μg of protein with further dialysis in PBS. The cell viability assay was conducted using free CRM197 at different concentrations, DOX, CRM197 with DOX, and DOX-loaded CRM197. DOX-loaded CRM197 along with CRM197 with the addition of DOX showed significant differences in cell viability compared to control wells. CRM197-
Results. DOX complexes have an evident inhibitory effect on epidermoid carcinoma cell growth and can be used as treatment against epithelial tumours, with CRM197 as a promising carrier for targeted drug delivery.
Conclusions. CRM197-DOX complexes show evident inhibition of epidermoid carcinoma cell growth. They can be used as treatment against epithelial tumours, especially those overexpressing the proHB-EGF and its receptors, EGFR1 and EGFR4, with CRM197 as a promising carrier for targeted drug delivery.
Key words: CRM197, doxorubicin, epidermoid carcinoma, targeted treatment
© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2024