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Background/Aims: Recent reports showed that proteasome subunit alpha type-7 (PSMA7) was overexpressed in colorectal cancer. To investigate the mechanism of PSMA7 in promotion of colorectal cancer, we screened for its interaction partners. Methods and Results: This study found that PSMA7 associated with nucleotide-binding oligomerization domain-containing protein 1 (NOD1) by yeast two-hybrid screening, co-immunoprecipitation (IP), and GST-pull down assay. As shown by Western blotting and ubiquitin assay, PSMA7 downregulated the expression of NOD1 in a proteasome-dependent manner. Overexpression of PSMA7 in HCT116 cells resulted in an inhibition of NOD1-mediated apoptosis and NF-κB activation, whereas knockdown of PSMA7 by RNA interference enhanced NOD1 activity. Conclusion: Our data suggest that PSMA7 is a negative regulator of the NOD1, and may promote tumor growth by its inhibitory role on NOD1.

Esophageal cancer is one of the leading causes of mortality worldwide. Although, surgery, radio- and chemotherapy are used to treat the disease, the identification of new drugs is crucial to increase the curative effect. The aim of the present study was to examine the chemotherapeutic sensitizing effect of nimotuzumab (h-R3) and cisplatin cytotoxic drugs cisplatin (DDP) and 5-fluorouracil (5-FU) on esophageal carcinoma cells with two different epidermal growth factor receptor (EGFR) expressions. The expression of EGFR was detected in the human EC1 or EC9706 esophageal squamous cell carcinoma cell line using immunohistochemistry. The inhibitory effect of DDP and 5-FU alone or combined with h-R3 on EC1 or EC9706 cell proliferation was detected using an MTT assay. Flow cytometry and the TUNEL assay were used to determine the effect of single or combined drug treatment on cell apoptosis. The results showed that the expression of EGFR was low in EC1 cells but high in EC9706 cells. The inhibitory effect of the single use of h-R3 on EC1 or EC9706 cell proliferation was decreased. The inhibitory effect between single use of h-R3 alone and combined use of the chemotherapy drugs showed no statistically significant difference (P>0.05) on the EC1 cell growth rate, but showed a statistically significant difference (a=0.05) on EC9706 cell growth rate. The results detected by flow cytometry and TUNEL assay showed that the difference between single use of h-R3 alone and the control group was statistically significant with regard to the EC1 apoptosis rate effect (P<0.05), but not statistically significant for EC9706 (P>0.05). However, statistically significant differences were identified in the apoptotic rate of EC9706 cells between the h-R3 combined chemotherapy group and single chemotherapy group (P<0.05), but not on in the EC1 chemotherapy group (P>0.05). In conclusion, the sensitization effect of h-R3 on chemotherapy drugs is associated with the expression level of EGFR in EC1 or EC9706 cells. The cell killing effect of the combined use of h-R3 with DDP and 5-FU showed no obvious synergistic effect compared to the single-drug group, but only an additive effect. [ABSTRACT FROM AUTHOR]