To observe the biological significance of p53 isoforms Δ133p53 expression by using subcutaneous xenograft tumor model of rmhTNF-MKN-45 in nude mice, and provide a new basis for the treatment of gastric cancer.

The subcutaneous xenograft model of nude mice was established with human gastric cancer MKN-45 cells.The mice were randomly divided into three groups: blank control group was intramuscular injected with normal saline, experimental group 1 was intramuscular injected with rmhTNF 16.7 IU, and experimental group 2 was intramuscular injected with rmhTNF 33.3 IU, 0.1 ml once a day, for 10 days continuously.After 14 days, the nude mice were sacrificed, the tumor tissue was removed, the tumor volume and tumor inhibition rate were recorded, and the mRNA expression levels of Δ133p53, p53 and MDM2 were detected by NRT-PCR.

rmhTNF had an inhibitory effect on MKN-45 nude mice(F=937.773, P<0.01). The inhibitory rates of 16.7 IU and 33.3 IU rmhTNF were 14.10% and 29.04% after treating 10 d; the inhibitory rates of 16.7 IU and 33.3 IU rmhTNF were 36.09% and 57.50% after treating 14 d, and showed dose-effect and time-dependent relationships.The nRT-PCR results showed that with the increase of rmhTNF dose, the relative expression levels of Δ133p53 mRNA in MKN-45 nude mice transplanted tumor were 1.021, 0.602 and 0.372(F=105.735, P<0.01). The relative expression levels of MDM2 mRNA were 1.087, 0.826 and 0.617(F=27.028, P<0.01), and the relative expression levels of p53 mRNA were 0.321, 0.580 and 0.872(F=25.963, P<0.01). The Δ133p53 expression level decreased gradually, which was positively related to MDM2(r=0.913, P<0.01), and negatively related to p53(r=-0.903, P<0.01). Δ133p53 protein expression levels: 0.714, 0.496, 0.348(F=38.755, P<0.01), MDM2 protein expression levels: 0.747, 0.630, 0.531(F=18.897, P<0.01), and decreased with the increase of rmhTNF dose.The expression level of p53 protein in the experimental group was 0.338, 0.525, 0.713, and increased with the increase of rmhTNF dose(F=17.596, P<0.01). Pearson linear correlation analysis results showed that Δ133p53 expression level decreased gradually, which was positively correlated with MDM2(r=0.961, P<0.01), and negatively correlated with p53(r=-0.891, P<0.01).

In the inhibitory effect of rmhTNF on human gastric cancer cell line MKN-45 xenograft tumor in nude mice, Δ133p53 antagonizes wild-type p53, and its anti-tumor pathway may be related to the regulation of p53-MDM2 expression pathway, and it may be an important target of gastric cancer therapy.