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Molecular and Cellular Biochemistry

, Volume 461, Issue 1–2, pp 151–158 | Cite as

5-FU preferably induces apoptosis in BRAF V600E colorectal cancer cells via downregulation of Bcl-xL

  • Tongfei Shi
  • Mohan Gao
  • Meihui He
  • Fengli Yue
  • Yawei Zhao
  • Madi Sun
  • Kan HeEmail author
  • Li ChenEmail author
Article

Abstract

Fluorouracil (5-FU) which has been widely used in postoperative adjuvant therapy in patients with colon cancer, remains the main backbone of combination treatment of patients with colon cancer. However, the efficacy of 5-FU alone in colorectal cancer patients with BRAFV600E is not clear. In this study, we demonstrated that BRAFV600E confers sensitivity to 5-FU in vitro and in vivo xenograft model, using the paired isogenic colorectal cancer cell lines RKO with either BRAF Wild Type (WT)(+/−) or mutant (Mut) (600E/–). Our results revealed 5-FU preferably induces marked apoptosis in BRAF-mutant colorectal cancer cells, through attenuating expression of Bcl-xL and activation caspase-3/9 pathway, eventually conferring the anti-tumor efficacy of 5-FU in vitro and in vivo. Meanwhile, expression of Bcl-xL remained unchanged in BRAF WT group after treatment of 5-FU, although low extent of anti-tumor activity of 5-FU still being observed. In conclusion, these results provided a better understanding of clinical outcome of 5-FU between BRAF WT and mutant colorectal cancer patients, and suggested the inhibition of Bcl-xL might present an alternative strategy to enhance the therapeutic efficacy of 5-FU in colorectal cancer patients with BRAF mutation.

Keywords

Colorectal cancer BRAF V600E 5-FU Apoptosis Bcl-xL 

Abbreviations

5-FU

Fluorouracil

MAPK

Mitogen-activated protein kinase

WT

Wild Type

Mut

Mutant

Notes

Acknowledgements

We thank Bert Vogelstein (Howard Hughes Medical Institute, Johns Hopkins University) for Isogenic RKO BRAF WT and V600E mutant cells. This work is supported by National Natural Science Foundation of China (81603136) and Jilin Provincial Commission of Health and Family Planning (2016J068).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal care and experiments were conducted in accordance with national and institutional policies for animal health and well-being. The experimental procedure was performed by the Animal Ethics Committee of College of Basic Medical Sciences at Jilin University.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, College of Basic Medical SciencesJilin UniversityChangchunChina
  2. 2.School of NursingJilin UniversityChangchunChina

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