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Combining α-Hederin with cisplatin increases the apoptosis of gastric cancer in vivo and in vitro via mitochondrial related apoptosis pathway.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2019 Dec; Vol. 120, pp. 109477. Date of Electronic Publication: 2019 Sep 25. - Publication Year :
- 2019
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Abstract
- Object: Cisplatin is a type of broad-spectrum anti-carcinogen that has been widely used in anti-gastric cancer therapy. Drug resistance prevails in gastric cancer therapy. α-Hederin has been reported to exert anti-tumour ability by inducing apoptosis in many cancers in vitro and in vivo. A combination chemotherapy regimen can improve the outcome of patients.<br />Methods: In the present study, we used a CCK-8 assay, Hoechst 33258 staining, Annexin V-PE/7-AAD, intracellular reactive oxygen species (ROS) measurement, mitochondrial membrane potential (MMP) assay kit and western blotting to detect apoptosis and mitochondrial function in gastric cancer (GC) cells. A xenograft tumour model in nude mice was used to evaluate the anti-tumour effects of cisplatin and α-Hederin in vivo.<br />Results: Combination treatment of cisplatin and α-Hederin increased the apoptotic effects in cisplatin-induced GC cell lines. In the xenograft mouse model, the combination of cisplatin and α-Hederin remarkably increased the tumour inhibition effect compared to either drug alone. Interestingly, combination of cisplatin and α-Hederin increased the expression of apoptosis-related proteins. Using in vitro experiments, we verified that the combination of cisplatin and α-Hederin increased the accumulation of ROS in GC cell lines and also reduced the MMP, thus inhibiting proliferation and promoting apoptosis in GC cells.<br />Conclusion: α-Hederin enhances cisplatin-induced anti-tumour effects in GC both in vitro and in vivo by promoting the accumulation of ROS and decreasing MMP. Our data strongly suggested that α-Hederin is a promising candidate for intervention in gastric cancer.<br /> (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Animals
Apoptosis Regulatory Proteins metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Humans
Membrane Potential, Mitochondrial drug effects
Mice
Mice, Inbred BALB C
Mice, Nude
Mitochondria metabolism
Oleanolic Acid pharmacology
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Stomach Neoplasms metabolism
Antineoplastic Combined Chemotherapy Protocols pharmacology
Apoptosis drug effects
Cisplatin pharmacology
Mitochondria drug effects
Oleanolic Acid analogs & derivatives
Saponins pharmacology
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 120
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 31562979
- Full Text :
- https://doi.org/10.1016/j.biopha.2019.109477