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Synergistic effects of 7-O-geranylquercetin and siRNAs on the treatment of human breast cancer.
- Source :
-
Life sciences [Life Sci] 2019 Jun 15; Vol. 227, pp. 145-152. Date of Electronic Publication: 2019 Apr 19. - Publication Year :
- 2019
-
Abstract
- Aims: To investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer.<br />Main Methods: Xenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice was measured by flow cytometer and living imaging sysytem, respectively. Cell viability was detected using CCK-8 assay. Cell apoptosis was determined by Hoechst33342 staining and AV-PI staining. Tumors bearing mice were administered with GQ by gavage, and/or with liposome CDO14 mediated siRNAs via tail intravenous injection. Expression levels of proteins and cytokines were detected by western blot and ELISA, respectively.<br />Key Findings: Liposome CDO14 could deliver siRNA to tumor effectively. Combination of GQ and siSuvi promoted the antiproliferation and pro-apoptosis effects of GQ or siSuvi to MCF-7 cells, and reduced the level of survivin and raised the level of caspase-7 in cells. GQ combining with siSuvi inhibited the growth of tumor, down-regulated the expression of survivin and up-regulated the expression of caspase-7 in tumor tissue. Similarly, GQ combining with siIL-10 inhibited the growth of tumor, decreased the level of IL-10 and increased the level of TNF-α. These results revealed that GQ enhanced the pro-apoptosis effect of siSuvi on tumor cells and the modulating effect of siIL-10 on tumor microenvironment.<br />Significances: Synergistic anti-tumor effect of GQ and siRNAs against breast cancer proved that chemical drugs combining with siRNAs is a promising antitumor strategy.<br /> (Copyright © 2019. Published by Elsevier Inc.)
- Subjects :
- Animals
Apoptosis drug effects
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Down-Regulation
Drug Synergism
Female
Gene Expression Regulation, Neoplastic genetics
Humans
Liposomes
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
Quercetin metabolism
Quercetin pharmacology
RNA, Small Interfering pharmacology
Transfection
Xenograft Model Antitumor Assays
Breast Neoplasms drug therapy
Quercetin analogs & derivatives
Survivin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 227
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31009625
- Full Text :
- https://doi.org/10.1016/j.lfs.2019.04.047