Inhibition of Beclin 1 expression enhances cisplatin-induced apoptosis through a mitochondrial-dependent pathway in human ovarian cancer SKOV3/DDP cells.
The purpose of this study was to determine the influence of autophagy on cisplatin-induced ovarian cancer SKOV3/DDP cell line death through regulation of the expression of the autophagy gene, Beclin 1, and to explore the potential mechanism underlying the relationship between autophagy and apoptosis. When compared with a blank control group, the proportion of apoptotic cells undergoing Beclin 1 interfering increased significantly after cisplatin treatment, accompanied by reduction in mitochondrial membrane potential, increase in activities of caspase-9/3 and cytoplasmic cytochrome C, elevation of Bax expression, and reduction in Bcl-2 expression. However, the proportion of apoptotic cells with Beclin 1 overexpression reduced. These findings suggest that Beclin 1 plays an important role in the regulation of potent antitumor activity through a mitochondrial-dependent pathway in SKOV3/DDP cell line, and inhibition of Beclin 1 expression may become a new target for the sensitization therapy of ovarian cancer with cisplatin.
Department of Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.
Yang
Y
Sun
Jia-hua
JH
Liu
Long
L
Jin
Yu-xia
YX
Sui
Li
L
Lai
Yin
Y
Yang
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D000071186:Beclin-1; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases; D002945:Cisplatin