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Inhibition of PDCD6 Induces Cell Proliferation and Reduces Apoptosis in Human Epithelial Ovarian Cancer Cells. Yan Huang, Xiaohua Wu Department of Gynecology, Cancer Center, Fudan University Yan Huang ( 310108197903152242 ) Correspondence: Xiaohua Wu. Backgrounds.
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Inhibition of PDCD6 Induces Cell Proliferation and Reduces Apoptosis in Human Epithelial Ovarian Cancer Cells Yan Huang, Xiaohua Wu Department of Gynecology, Cancer Center, Fudan University Yan Huang (310108197903152242) Correspondence: Xiaohua Wu
Backgrounds Ovarian epithelial cancer is the leading killer among all gynecological malignancies. Recent findings suggested that apoptosis and apoptosis-linked genes may play an important role in the development and progression of ovarian cancer (la Cour JM, et al. Mol Oncol. 2008). Programmed cell death gene 6 (PDCD6), also known as apoptosis-linked gene-2 (ALG-2), is a 22 kDa penta-EF-hand type Ca2+-binding protein that was first reported by Vito in 1996. It is well recognized as an apoptotic mediator because PDCD6 expression is required for apoptosis following numerous death stimuli (Vito P, et al. Science. 1996).
Methods BrdU Poliferation Design of siRNA and construction of recombi-nant plasmids RT-PCR, Western blot Flow cytometry Transfection SKOV-3 and OVCAR-3 Apoptosis RT-PCR, Western blot Flow cytometry Cell cycle RT-PCR, Western blot Effects of cisplatin on ovarian cancer cells SKOV-3 and OVCAR-3 BrdU, Flow cytometry Poliferation Apoptosis PDCD6 RT-PCR, Western blot
Results RNAi inhibited PDCD6 expression in ovarian cancer cells
Inhibition of PDCD6 prohibited apoptosis and increased cell proliferation
PDCD6 RNAi partly blocked the apoptotic effect and the anti-proliferative effect induced by cisplatin
Conclusions • 1. Inhibition of PDCD6 by RNAi induced cell proliferation and cell cycle in SKOV-3 and OVCAR-3 cells by up-regulating cyclin D1, cyclin B1, cyclin E, and proliferating cell nuclear antigen (PCNA). • 2. Inhibition of PDCD6 by RNAi reduced apoptosis in SKOV-3 and OVCAR-3 cells by decreasing cleaved caspase-3, cleaved caspase-7, cleaved caspase-8, Bax, death receptor 5 (DR5)and death receptor 4(DR4) and increasing Bcl-2.
3. Cisplatin increased cell apoptosis and prohibited cell proliferation while the mRNA and protein expression of PDCD6 was up-regulated. • 4. PDCD6 RNAi partly blocked the apoptotic effect and the anti-proliferative effect induced by cisplatin. Cisplatin may inhibit proliferation and increase apoptosis partly through PDCD6. • 5. PDCD6 plays an important role in the promotion and progression of ovarian cancer. PDCD6 is a candidate as a new target for ovarian cancer treatment.