Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

Lactoferrin improves hepatic pyroptosis in mice after irradiation

Objective:To investigate the effects of lactoferrin(Lf)on hepatic pyroptosis(an inflammatory form of programmed cell death)in mice exposed to radiation.Methods:A total of thirty-six BALB/c male mice were randomly divided into four groups,namely the control group,5 Gy group,5 Gyþ2 mg Lf group,and 5 Gyþ4 mg Lf group.The mice were administered whole-body ionizing radiation using a PRIMUS accelerator,with a single dose of 5 Gy and an absorbed dose rate of 2.0 Gy/min at a source-skin distance of 100 cm.Lf solution was intraperitoneally injected into the mice 2 h before and per day after radiation.The mice were sacrificed 1,3,and 9 d after radiation,and their livers were used for histopathologic examination,immunohistochemistry analysis,and Western blot analysis for absent in melanoma 2(AIM2)inflammasome pathway.Results:Histopathologic examination showed the disorder of the hepatocellular structure and the accumulation of inflammatory cells after radiation.Lf intervention inhibited hepatocellular proliferation and decreased the infiltration of inflammatory cells.Immunohistochemistry analysis indicated that AIM2 overexpression was significantly attenuated by 4 mg of Lf(t=3.065,P<0.05)3 d after radiation and by 2 mg and 4 mg of Lf(t=4.032,t=2.786,P<0.05)9 d after radiation.Western blot analysis showed that Lf downregulated the hepatic overexpression of AIM2,apoptosis-associated speck-like protein containing a caspase activation and recruitment domain(ASC),IL-1β,and IL-18.2 mg of Lf significantly downregulated the abovementioned protein expression 3 d(t=7.934,4.092,5.193,2.916,P<0.05)and 9 d after radiation(t=5.016,3.882,9.528,P<0.05 for AIM2,ASC,IL-1β).Conclusions:Lf intervention suppressed the hepatic pyroptosis in mice exposed to ionizing radiation by downregulating the protein expression of AIM2 inflammasome.