Co-downregulation of GRP78 and GRP94 Induces Apoptosis and Inhibits Migration in Prostate Cancer Cells

Tong Lu; Yue Wang; Kang Xu; Zhijun Zhou; Juan Gong; Yingang Zhang; Hua Gong; Qiang Dai; Jun Yang; Biao Xiong; Ze Song; Gang Yang

doi:10.1515/biol-2019-0043

Co-downregulation of GRP78 and GRP94 Induces Apoptosis and Inhibits Migration in Prostate Cancer Cells

Open Life Sci. 2019 Jul 22:14:384-391. doi: 10.1515/biol-2019-0043. eCollection 2019 Jan.

Authors

Tong Lu¹, Yue Wang², Kang Xu¹, Zhijun Zhou¹, Juan Gong¹, Yingang Zhang¹, Hua Gong¹, Qiang Dai¹, Jun Yang¹, Biao Xiong¹, Ze Song¹, Gang Yang¹

Affiliations

¹ Department of Urology, The First People's Hospital of Tianmen City, East No.1, Renmin Avenue, Tianmen City, Hubei 431700, P.R.China.
² Sinopharm Wuhan Plasma-derived Biotherapies Co. Ltd., No.1 attached No.1, Zhengdian Gold Industrial Park Road, Jiangxia District, Wuhan, Hubei 430070, P.R.China.

Abstract

Background: Both glucose-regulated protein 78 kDa (GRP78) and glucose-regulated protein 94 kDa (GRP94) are important molecular chaperones that play critical roles in maintaining tumor survival and progression. This study investigated the effects in prostate cancer cells following the downregulation of GRP78 and GRP94.

Methods: RNA interference was used to downregulate GRP78 and GRP94 expression in the prostate cancer cell line, PC-3. The effects on apoptosis and cell migration was examined along with expression of these related proteins.

Results: Small interfering RNAs targeting GRP78 and GRP94 successfully down-regulated their expression. This resulted in the induction of apoptosis and inhibition of cell migration. Preliminary mechanistic studies indicated that caspase-9 (cleaved) and Bax expression levels were upregulated while Bcl-2 and vimentin expression levels were downregulated.

Conclusion: Co-downregulation of GRP78 and GRP94 expression induces apoptosis and inhibits migration in prostate cancer cells.

Keywords: GRP78; GRP94; apoptosis; migration; prostate cancer.