Published online Aug 15, 2020. doi: 10.4251/wjgo.v12.i8.877
Peer-review started: May 12, 2020
First decision: June 15, 2020
Revised: June 20, 2020
Accepted: July 26, 2020
Article in press: July 26, 2020
Published online: August 15, 2020
Processing time: 91 Days and 22.3 Hours
The systemic toxicity and drug resistance of tumor cells are still two major problems in cancer chemotherapy. The chemotherapeutic drug 5-fluorouracil (5-FU) can inhibit the synthesis of adenylate synthetase and interfere with the synthesis of DNA in tumor cells. The effect of 5-FU is not ideal due to the chemoresistance in colon carcinoma patients treated with 5-FU.
Interleukin (IL)-1 and nuclear factor kappa-B (NF-κB) show a cyclic relationship, which leads to persistent activation of NF-κB in tumor cells. In Kras and p53 gene mutant mice, we found that the activity of NF-κB was downregulated by inhibiting the IL-1 receptor, which could effectively slow tumor growth.
The aim of this study was to determine whether treatment with 5-FU combined with IL-1 receptor antagonist can increase the chemosensitivity to 5-FU by decreasing the activation of the NF-κB pathway and reducing the proliferation of colon cancer cells. The results obtained provide a theoretical basis for clinical adjuvant chemotherapy.
The expression of phosphorylated P65 in the COLO205, SW620, and HCT116 cell lines was significantly higher than that in the NCM460 cell line, as shown by Western blot assays. We used a xenograft nude mouse model to demonstrate the downregulation of the NF-κB pathway by blocking the NF-κB-regulated IL-1α feedforward loop, which could increase the efficacy of chemotherapeutic agents in inhibiting colon tumor cell growth.
IL-1RA combined with 5-FU showed stronger inhibition of the proliferation of the SW620 and HCT116 cell lines than 5-FU treatment. IL-1RA combined with 5-FU treatment had a greater effect in extending the survival time of the tumor-bearing nude mice than 5-FU single therapy.
IL-1 receptor antagonist combined with 5-FU has a stronger inhibitory effect on the proliferation of colon cancer cells than 5-FU alone due to the blockade of IL-1.
These results could provide an adjuvant chemotherapy strategy for the clinic and provide a theoretical basis for neoadjuvant chemotherapy.