4.4 Article

Involvement of ribosomal protein L11 expression in sensitivity of gastric cancer against 5-FU

Journal

ONCOLOGY LETTERS
Volume 19, Issue 3, Pages 2258-2264

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2020.11352

Keywords

5-Fluorouracil; gastric cancer; drug sensitivity; RPL11; P53 pathway

Categories

Funding

  1. JSPS KAKENHI [JP17J05291, JP15K10311, JP15K10338, JP22501047, JP16K07121, JP17K10871, JP17K07221, JP18K06732]
  2. Molecular Profiling Committee
  3. Ministry of Education, Culture, Sports, Science and Technology, Japan (JSPS KAKENHI) [JP 16H06276]
  4. Takeda Medical Foundation
  5. Shinnihon Foundation of Advanced Medical Treatment Research
  6. Kodama Memorial Fund for Medical Research
  7. Mochida Memorial Foundation for Medical and Pharmaceutical Research
  8. Foundation for Promotion of Cancer Research in Japan
  9. Suzuken Memorial Foundation
  10. Shimabara Science Promotion Foundation
  11. Astellas Foundation for Research on Metabolic Disorders

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5-Fluorouracil (5-FU) is widely used in the treatment of various types of solid cancer. Our study showed that ribosomal protein L11 (RPL11) was a crucial factor affecting sensitivity of gastric cancer to 5-FU, implying that RPL11 expression is a potential biomarker for predicting 5-FU sensitivity. Kaplan-Meier survival analysis indicated that high RPL11 expression in gastric cancer patients treated with 5-FU was significantly associated with good prognosis. It was therefore investigated whether RPL11 affected the sensitivity of gastric cancer against 5-FU using four human gastric cancer cell lines, MKN45 (wild-type TP53 gene), NUGC4 (wild-type), MKN7 (mutated), and KE39 cells (mutated). In vitro assays demonstrated that RPL11 knockdown in gastric cancer cell lines carrying the TP53 wild-type gene attenuated 5-FU-induced cell growth suppression and activation of the P53 pathway, but not in cells carrying mutated TP53, suggesting that 5-FU suppresses tumor progression via RPL11-mediated activation of the P53 pathway in gastric cancer. The present study provides a potential therapeutic strategy for improving 5-FU resistance in gastric cancer by elevating RPL11 expression.

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