Chemosensitization of HT29 and HT29-5FU Cell Lines by a Combination of a Multi-Tyrosine Kinase Inhibitor and 5FU Downregulates ABCC1 and Inhibits PIK3CA in Light of Their Importance in Saudi Colorectal Cancer.
Adult
Aged
Antimetabolites, Antineoplastic
/ pharmacology
Apoptosis
/ drug effects
Chromones
/ pharmacology
Class I Phosphatidylinositol 3-Kinases
/ antagonists & inhibitors
Colorectal Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
/ drug effects
Drug Synergism
Female
Fluorouracil
/ pharmacology
HCT116 Cells
HT29 Cells
Humans
Male
Middle Aged
Morpholines
/ pharmacology
Multidrug Resistance-Associated Proteins
/ antagonists & inhibitors
Phosphoinositide-3 Kinase Inhibitors
/ pharmacology
Protein Kinase Inhibitors
/ pharmacology
Saudi Arabia
/ epidemiology
5FU
ABCC1
PIK3CA
Saudi colorectal cancer
drug resistance
kinase pathway profiling
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
11 Jan 2021
11 Jan 2021
Historique:
received:
09
12
2020
revised:
30
12
2020
accepted:
07
01
2021
entrez:
14
1
2021
pubmed:
15
1
2021
medline:
11
9
2021
Statut:
epublish
Résumé
Colorectal cancer (CRC) remains one of the main causes of death worldwide and in Saudi Arabia. The toxicity and the development of resistance against 5 fluorouracil 5FU pose increasing therapeutic difficulties, which necessitates the development of personalized drugs and drug combinations. First, to determine the most important kinases and kinase pathways, and the amount of ABC transporters and KRAS in samples taken from Saudi CRC patients. Second, to investigate the chemosensitizing effect of LY294002 and HAA The PamChip The kinase activity profiling highlighted the importance of the PI3K/AKT, MAPK, and the growth factors pathways in the Saudi CRC samples. PIK3CA was the most overexpressed, and it was associated with increased level of mutated KRAS and the three ABC transporters, especially ABCC1 in the Saudi samples. Next, combining HAA We have combined the PamChip kinase profiling of Saudi CRC samples with in vitro drug combination studies in four CRC cells, highlighting the importance of targeting PIK3CA and ABCC1 for Saudi CRC patients, especially given that the overexpression of PIK3CA mutations was previously linked with the lack of activity for the anti-EGFRs as first line treatment for CRC patients. The combination of HAA
Identifiants
pubmed: 33440689
pii: molecules26020334
doi: 10.3390/molecules26020334
pmc: PMC7827067
pii:
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Chromones
0
Morpholines
0
Multidrug Resistance-Associated Proteins
0
Phosphoinositide-3 Kinase Inhibitors
0
Protein Kinase Inhibitors
0
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
31M2U1DVID
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Fluorouracil
U3P01618RT
multidrug resistance-associated protein 1
Y49M64GZ4Q
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : King Abdulaziz City for Science and Technology
ID : 13-MED873-10
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