Troxerutin (TXN) potentiated 5-Fluorouracil (5-Fu) treatment of human gastric cancer through suppressing STAT3/NF-κB and Bcl-2 signaling pathways.
Biomed Pharmacother
; 92: 95-107, 2017 Aug.
Article
de En
| MEDLINE
| ID: mdl-28531805
ABSTRACT
Gastric cancer still presents a significant problem for public health worldwide. Troxerutin (TXN), a flavonoid present in tea, coffee, cereal grains, and a variety of fruits and vegetables, exhibits various pharmacological and biological activities in vitro and in vivo. We investigated the ability of TXN to reverse the in vitro and in vivo drug resistance of human gastric cancer cells, which were resistant to treatment of 5-Fluorouracil (5-FU). 5-Fu is a pyrimidine analog, which is widely used in the treatment of cancers. Here, we found the growth inhibitory effects of TXN on human gastric cancer cell, resistant to 5-FU. TXN and 5-FU co-treatment resulted in a dose-dependent suppression of the cell proliferation. Decreasing of phosphorylated signal transducers and activation of transcription 3 (STAT3) was included in suppression of p65 by TXN with 5-FU in combination. Additionally, the presence of TXN sensitized gastric cancer cells resistant to 5-FU to 5-FU-induced apoptosis by suppressing Bcl-2. The pro-apoptotic proteins of Bax and Bid were up-regulated, accompanied with Caspase cleavage, leading to apoptosis. Moreover, in mice xenograft models, the combined therapy inhibited tumor growth compared to the TXN or 5-FU treatment alone. Our data indicated a novel therapeutic strategy to potentiate 5-FU-induced anti-tumor effect in gastric cancer cells with resistance to 5-FU by TXN through suppression of p-STAT3/NF-κB (p65 and p50) and Bcl-2.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs de l'estomac
/
Transduction du signal
/
Protocoles de polychimiothérapie antinéoplasique
/
Protéines proto-oncogènes c-bcl-2
/
Facteur de transcription STAT-3
/
Fluorouracil
/
O-(bêta-Hydroxyéthyl)rutosides
Type d'étude:
Clinical_trials
/
Prognostic_studies
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Biomed Pharmacother
Année:
2017
Type de document:
Article
Pays d'affiliation:
Chine