TY - JOUR
T1 - The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth
AU - Begimbetova, Dinara
AU - Kukanova, Assiya
AU - Fazyl, Fatima
AU - Manekenova, Kenzhekyz
AU - Omarov, Talgat
AU - Burska, Agata N.
AU - Khamijan, Medina
AU - Gulyayev, Alexandr
AU - Yermekbayeva, Bakytgul
AU - Makishev, Abay
AU - Saliev, Timur
AU - Batyrbekov, Kanat
AU - Aitbayev, Chokan
AU - Spatayev, Zhanat
AU - Sarbassov, Dos
N1 - Publisher Copyright:
© 2022 Dinara Begimbetova et al.
PY - 2022
Y1 - 2022
N2 - Background. Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective. To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods. In this study, we examined the effectiveness of ATO and D-VC on xenograft models - AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results. The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.
AB - Background. Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective. To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods. In this study, we examined the effectiveness of ATO and D-VC on xenograft models - AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results. The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.
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U2 - 10.1155/2022/9426623
DO - 10.1155/2022/9426623
M3 - Article
C2 - 36619305
AN - SCOPUS:85145967438
SN - 2314-6133
VL - 2022
JO - BioMed Research International
JF - BioMed Research International
M1 - 9426623
ER -
