Objective To establish a mouse colon 26 (C26) cachexia model and observe the time-course
changes of blood parameters and inflammatory factors.
Methods The C26 tumor fluid was inoculated subcutaneously into the right flank
of BALB/c mice. When the tumor grew to a diameter of approximately10 mm, the mice were sacrificed to take out
the tumor, and the tumor homogenate was diluted
according to 1:60 after homogenization, and then the cell
liquid was injected subcutaneously at 200 μL/mouse. After the tumor cells were
transplanted into the mice, the body weight and tumor volume were examined. The
animals were sacrificed on 12 d and 18 d after tumor inoculation, and then brown
adipose tissue (BAT), epididymal white adipose tissue (WAT), quadriceps,
gastrocnemius muscle, spleen, thymus and tumors were extracted for detection.
After the tissue samples were obtained, the plasma samples were taken for
cytokine detection. Blood cells were collected for differential analysis of
blood types and CD4+/CD8+ lymphocytes. Pathological
sections and HE staining were performed on adipose tissue.
Results After the C26
tumor fluid was inoculated subcutaneously in BALB/c mice, the body weights of
the mice in the tumor group were decreased significantly on 12 d and 18 d after
tumor inoculation. The weights of BAT were decreased significantly at
12 d and 18 d, the
lipid droplets in BAT became significantly smaller, and the cytoplasmic content
of the lipid droplets were increased. The weights of the epididymis WAT were basically
unchanged as compared with the control at 12 d after tumor inoculation, but the
weights were significantly reduced after 18 d, and the lipid droplets of WAT
were slightly smaller after 12 d of tumor inoculation, and significantly
smaller at 18 d, and WAT was browned. The weights of the quadriceps and
gastrocnemius muscles in the tumor group were also reduced as compared with the
control group on 12 d or 18 d after tumor inoculation. The spleen volumes of
the animals in the tumor group became larger, and the spleen weights were also
increased significantly. Thymus weights were decreased at 12 d or 18 d after
tumor inoculation. The results from flow cytometry showed that there was no
statistically significant difference in the number of CD4+/CD8+ cells in the blood of mice for the control and tumor group. After 12 d of
inoculation, the content of IL-6 inplasma was increased significantly, and after 18 d of inoculation, the
concentration of IFN-γ was decreased significantly, and the contents of IL-1,
TNF-α and IL-6 were increased significantly. After 12 d of tumor inoculation,
the RBC, HGB, HCT%, MCH, PLT and PCT% in the tumor group were significantly
lower than those in the control group, and the MON% was also significantly higher
than that in the control group. After 18 days of tumor inoculation, RBC, HGB,
HCT%, LYM% and BAS% were significantly decreased as compared with the control
group, RDW%, WBC, LYM, MON, NEU, MON% and NEU% were significantly increased as
compared with the control group.
Conclusion We successfully construct a mouse model of C26
cachexia, which is characterized by weight loss, muscle and fat loss, browning
of WAT, enlarged spleen, shrinking thymus, obvious changes in blood count,
etc., and especially the changes of IL-6 inthe early stage are noteworthy. The
establishment and validation of this model provides a reliable basis and
reference for us to study cancer cachexia.