PUBLICATION
Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect
- Authors
- Chang, Y.Y., Lin, H.J., Hsiao, L.C., Lin, Y.F., Chang, C.S., Liu, D.Z.
- ID
- ZDB-PUB-211211-5
- Date
- 2021
- Source
- PLoS One 16: e0260533 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Zebrafish
- Docetaxel/pharmacology*
- Female
- Animals
- Cell Survival/drug effects
- Cell Line, Tumor
- Breast Neoplasms/drug therapy
- Breast Neoplasms/metabolism*
- Doxorubicin/pharmacology*
- Glucosides/pharmacology*
- Drug Synergism
- Humans
- Drug Resistance, Neoplasm/drug effects*
- ATP Binding Cassette Transporter, Subfamily B/metabolism
- Cell Proliferation/drug effects
- Gene Expression Regulation, Neoplastic/drug effects
- Stilbenes/pharmacology*
- MCF-7 Cells
- PubMed
- 34874967 Full text @ PLoS One
Citation
Chang, Y.Y., Lin, H.J., Hsiao, L.C., Lin, Y.F., Chang, C.S., Liu, D.Z. (2021) Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect. PLoS One. 16:e0260533.
Abstract
Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4'-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping