Combining α-Hederin with cisplatin increases the apoptosis of gastric cancer in vivo and in vitro via mitochondrial related apoptosis pathway

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.

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.

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.

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.

Keywords: Cisplatin; Gastric cancer; Mitochondria-related apoptosis; Reactive oxygen species; α-Hederin.