PhD Scientific Days 2024

Poster Session A - Molecular Medicine 1.

Gene expression changes in colitis-associated colorectal cancer progression in animals with different hypoxia resistance

Text of the abstract

Introduction
One of the factors in the development of colitis-associated colorectal cancer (CAC) is inflammation, which is largely associated with hypoxia. CAC induced by administration of azoxymethane (AOM) and several cycles of dextran sulfate sodium (DSS) consumption is one of the main experimental models to study this disease. We have previously revealed that animals with different hypoxia resistance differ in the severity of acute and chronic ulcerative colitis induced by DSS – susceptible (S) mice demonstrate more pronounced acute and chronic colitis in comparison to tolerant (T) ones.

Aims
To study gene expression changes during CAC in animals with different hypoxia resistance.

Method
The study was performed on male C57Bl/6 mice (age 1.5-2 months, n=50). Resistance to hypoxia was determined once in a ventilated decompression chamber by creating conditions equivalent to a critical “altitude” of 10 000 m by “gasping time” (GT) before assuming the lateral position. The mice were further divided into T (GT>10 min, n=13) and S (GT<3 min, n=11). One month later, animals of the experimental groups (n(T)=8, n(S)=6) were injected once intraperitoneally with AOM (10 mg/kg), then consumed 3 cycles of DSS, followed after by water only. Mice of control groups (n(T)=5, n(S)=5) were intraperitoneally injected with 0.9% NaCl, then consumed only water. On the 141st day the animals were removed from the experiment. The colon and tumor fragments were obtained from animals to analyze the expression of Hif1a, Epas1, Hif3a, Vegf, Nfkb, Il1b, Il6, Tnfa, Il10 genes by RT-PCR.

Results
The initial expression of Hif3a, Nfkb and Il10 was higher in the S mice of control group compared to T. On the 141st day of the experiment, only in S mice tumors detected increased expression of Tnfa, while only in T animals tumors demonstrated increased expression of Nfkb, Il6 and decreased Epas1 compared to control. Furthermore, higher expression levels of Hif3a, Vegf, Tnfa, Il10 and Tgfb in tumor tissues were observed in S animals compared to T.

Conclusion
The process of experimental CAC development in susceptible to hypoxia mice in comparison to tolerant was characterized by faster rate, as well as high expression of Hif3a, Vegf, Tnfa, Il10 and Tgfb mRNAs in tumors.

Funding
This work was financially supported by the Russian Science Foundation (№23-25-00294).