Patrinia scabiosaefolia Inhibits Growth of 5-FU-Resistant Colorectal Carcinoma Cells via Induction of Apoptosis and Suppression of AKT Pathway.
10.1007/s11655-018-3002-6
- Author:
Si-Zhou HUANG
1
;
Wang-Yu LIU
2
;
Yue HUANG
2
;
A-Ling SHEN
2
;
Li-Ya LIU
2
;
Jun PENG
3
Author Information
1. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
2. Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
3. Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. pjunlab@hotmail.com.
- Publication Type:Journal Article
- Keywords:
5-fluorouracil resistance;
AKT pathway;
Chinese medicine;
Patrinia scabiosaefolia;
colorectal cancer
- MeSH:
Apoptosis;
drug effects;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Cell Survival;
drug effects;
Colorectal Neoplasms;
drug therapy;
pathology;
Drug Resistance, Neoplasm;
drug effects;
Fluorouracil;
pharmacology;
therapeutic use;
Humans;
Patrinia;
chemistry;
Phosphorylation;
drug effects;
Proto-Oncogene Proteins c-akt;
metabolism;
Signal Transduction;
drug effects;
Tumor Stem Cell Assay;
bcl-2-Associated X Protein;
metabolism
- From:
Chinese journal of integrative medicine
2019;25(2):116-121
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the effects of ethanol extract of Patrinia scabiosaefolia (EEPS) on chemo-resistance of colorectal cancer cells (CRC) and explore the possible molecular mechanisms.
METHODS:5-fluorouracil (5-FU)-resistant human colorectal carcinoma cell line (HCT-8/5-FU) and its parental cells HCT-8 were treated with EEPS (0, 0.25, 0.50, 1 or 2 mg/mL), or 5-FU (0, 100, 200, 400, 800 or 1600 μmol/L). The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the cell viability. Cell density was observed by phase-contrast microscope, cell counting and colony formation assay were used to determine the cell proliferation of HCT-8/5-FU cells treated with 0, 0.5, 1 or 2 mg/mL EEPS. Cell apoptosis was determined by Hoechst staining. Western-blot was performed to detect the phosphorylation of AKT as well as the protein expression level of B-cell CLL/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).
RESULTS:Compared with HCT-8 cells, MTT assay results indicated that HCT-8/5-FU cells were resistant to 5-FU treatment (P<0.05), and sensitive to EEPS treatment (P>0.05). Moreover, compared with untreated HCT-8/5-FU cells, 1 and 2 mg/mL of EEPS treatment significantly reduced cell density, cell number, inhibited cell survival (P<0.05), and induced apoptosis in HCT-8/5-FU cells. Furthermore, 1 and 2 mg/mL of EEPS significantly decreased the phosphorylation level of p-AKT and Bcl-2 protein expression, and increased the expression of Bax protein (P<0.05).
CONCLUSION:EEPS is a promising therapeutic agent that may overcome chemo-resistance in cancer cells, likely through suppression of the AKT pathway and promotion of cancer cell apoptosis.