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Interleukin-1 receptor antagonist enhances chemosensitivity to fluorouracil in treatment of Kras mutant colon cancer.
Yan, Yan; Lin, Hong-Wei; Zhuang, Zhuo-Nan; Li, Ming; Guo, Sen.
Afiliação
  • Yan Y; Department of Operating Room, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China.
  • Lin HW; Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital School of Clinical Medicine, Tsinghua University, Beijing 102200, China.
  • Zhuang ZN; Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital School of Clinical Medicine, Tsinghua University, Beijing 102200, China.
  • Li M; Department of General Surgery, Zouping Traditional Chinese Medicine Hospital, Zhouping 256200, Shandong Province, China.
  • Guo S; Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China. guosen4321@163.com.
World J Gastrointest Oncol ; 12(8): 877-892, 2020 Aug 15.
Article em En | MEDLINE | ID: mdl-32879665
ABSTRACT

BACKGROUND:

Kras mutant colon cancer shows abnormal activation of the nuclear factor kappa-B (NF-κB) pathway, resulting in the proliferation of tumor cells. Treatment with fluorouracil (5-FU) might not achieve the expected inhibition of proliferation of malignant cells based on the fluorouracil-induced activation of the NF-κB pathway.

AIM:

To detect whether interleukin (IL)-1 receptor antagonist (IL-1RA) could increase the chemosensitivity to 5-FU by decreasing the activation of the NF-κB pathway and reducing the proliferation of colon cancer cells.

METHODS:

Western blot analysis was performed to detect the persistent activation of the NF-κB pathway in colon cancer cell lines. Reverse transcription-polymerase chain reaction was used to detect the IL-1RA-reduced expression levels of IL-6, IL-8, IL-17, IL-21 and TLR4 in colon cancer cell lines. 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 tumor cell growth.

RESULTS:

IL-1 receptor antagonist could decrease the expression of IL-1α and IL-1ß and downregulate the activity of the NF-κB pathway in Kras mutant colon cancer cells. Treatment with 5-FU combined with IL-1RA could increase the chemosensitivity of the SW620 cell line, and decreased expression of the TAK1/NF-κB and MEK pathways resulted in limited proliferation in the SW620 cell line.

CONCLUSION:

Adjuvant chemotherapy with IL-1RA and 5-FU has a stronger effect than single chemotherapeutic drugs. IL-1RA combined with fluorouracil could be a potential neoadjuvant chemotherapy in the clinic.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: World J Gastrointest Oncol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: World J Gastrointest Oncol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China