Assay the Cytotoxicity of Agents Targeting K-RAS Oncogene in Treatment Colorectal Cancer
الباحث الأول:
Zahraa F. Fleih
الباحثين الآخرين:
Bashaer M. MuhammadBaqir, Sarah K. Obayes, Rawaa H. Shareef
المجلة:
Surgery, Gastroenterology and Oncology
تاريخ النشر:
31 يناير، 2025
مختصر البحث:
Background: Cancer is considered as the second leading cause of death and the most popular
kind of gastrointestinal cancer is colorectal cancer that resulted from genetic alterations
progressed during a lifetime. In human cancer, the most frequen…
Background: Cancer is considered as the second leading cause of death and the most popular
kind of gastrointestinal cancer is colorectal cancer that resulted from genetic alterations
progressed during a lifetime. In human cancer, the most frequently mutated oncogenes but have
not produced to therapeutic attack are RAS genes (KRAS, NRAS and HRAS). Methotrexate is a
cytotoxic chemotherapeutic agent, as it acts on cell cycle. Aims: This study aims to investigate
the cytotoxicity effect MEX2R and MEX2O in human colorectal cells and to compare its action
with MTX. MEX2R and MEX2O investigational agents as K-RAS oncogene blocker which inhibits
the cell proliferation by targeting the cell cycle.
Methods: LST 174 colorectal cell line was grown in RPMI- 1640 media supplement with
10% heat inactivated fetal bovine serum and antibiotic 100IUs/ml penicillin with 100 μg/ml
streptomycin. The cells were incubated with agents and drugs for 24 hours. Cells were
inoculated in 96-well microtiter plate (105 cells/well) for 48 hrs. The final concentration of the
solvent never exceeded 0.1%. Triplicates were prepared for each individual dose. Color intensity
was measured in an ELISA reader. The viability and inhibition % of cancer cell line after the spec-
ified time were then detected and the concentration that inhibit 50% of cell viability (IC50) was
fitted and calculated.
Results: There was no significant increase (P> 0.05) in cell growth inhibition as compared with
control group at conc. (0.5,1,5 μg/ml) of MEX2R, while there was a highly significant increase
(P≤0.05) in inhibition of growth LST174 cells in conc. (25, 125,625 μg/ml). Additionally, the
conc.of drug that needed to inhibit a biological process or response by 50% (IC50) is about 411
mg/ml . The result showed that MEX2O has significant difference (P≤0.05) in LST174 cells
growth inhibition in all concentrations (0.5,1.5.25,125,625 & 1000 μg/ml) when compared with
control(untreated) group. While, the concentration of drug that needed to inhibit a biological
process or response by 50% (IC50) is about 317.69 mg/ml. Also, the result showed that MTX
has significant increase (P≤0.05) in growth inhibition of LST174 cells in all concentrations
(0.5,1,5,25,125,625,1000 μg/ml) when compared with control group. While, the results
showed that the conc. of drug that needed to inhibit a biological process or response by 50%
(IC50) is about 803.8 mg/ml.
Conclusion: MEX2R and MEX2O might be have a greater value in the treatment of this type of
cancer than MTX as they act on the cell cycle as the tested drugs MEX2R & MEX2O acted on
the cell cycle by targeting one of the main troubles that interfere with treatment of colorectal
cancer which is K-RAS gene mutation and inhibit the cell proliferation.
Keywords: Colorectal cancer, MEX2R, MEX2O, MTX, K-RAS gene mutation
