5-FU preferably induces apoptosis in BRAF V600E colorectal cancer cells via downregulation of Bcl-x.sub.L

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 stu...

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Veröffentlicht in:Molecular and cellular biochemistry 2019-11, Vol.461 (1-2), p.151
Hauptverfasser: Shi, Tongfei, Gao, Mohan, He, Meihui, Yue, Fengli, Zhao, Yawei, Sun, Madi, He, Kan
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container_issue 1-2
container_start_page 151
container_title Molecular and cellular biochemistry
container_volume 461
creator Shi, Tongfei
Gao, Mohan
He, Meihui
Yue, Fengli
Zhao, Yawei
Sun, Madi
He, Kan
description 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-x.sub.L and activation caspase-3/9 pathway, eventually conferring the anti-tumor efficacy of 5-FU in vitro and in vivo. Meanwhile, expression of Bcl-x.sub.L 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-x.sub.L might present an alternative strategy to enhance the therapeutic efficacy of 5-FU in colorectal cancer patients with BRAF mutation.
doi_str_mv 10.1007/s11010-019-03598-5
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subjects Adjuvant treatment
Antimitotic agents
Antineoplastic agents
Apoptosis
Cancer
Cancer cells
Colorectal cancer
Gene mutations
title 5-FU preferably induces apoptosis in BRAF V600E colorectal cancer cells via downregulation of Bcl-x.sub.L
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