J Cancer 2019; 10(25):6269-6277. doi:10.7150/jca.34859

Research Paper

GV1001 inhibits cell viability and induces apoptosis in castration-resistant prostate cancer cells through the AKT/NF-κB/VEGF pathway

Yong Hyun Park1,2, Ae Ryang Jung1,2, Ga Eun Kim1,2, Mee Young Kim1,2, Jae Woo Sung1, Dongho Shin1, Hyuk Jin Cho1, U-Syn Ha1,2, Sung-Hoo Hong1,2, Sae Woong Kim1, Ji Youl Lee1,2✉

1. Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
2. Cancer Research Institute, College of Medicine, The Catholic University of Korea

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Citation:
Park YH, Jung AR, Kim GE, Kim MY, Sung JW, Shin D, Cho HJ, Ha US, Hong SH, Kim SW, Lee JY. GV1001 inhibits cell viability and induces apoptosis in castration-resistant prostate cancer cells through the AKT/NF-κB/VEGF pathway. J Cancer 2019; 10(25):6269-6277. doi:10.7150/jca.34859. Available from http://www.jcancer.org/v10p6269.htm

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Abstract

Purpose: We examined the effect of GV1001 in castration castration-resistant prostate cancer (CRPC) cell growth and invasion and explored the potential molecular mechanisms of action.

Materials and Methods: The in vitro anti-cancer effects of GV1001 in CRPC cells were examined using cell viability assay, TUNEL assay, and flow cytometry analysis. To evaluate the effects of GV1001 on different steps of angiogenesis, wound healing assay, transwell invasion assay, endothelial cell tube formation assay, and western blot analysis were performed. Finally, the anti-cancer effects of GV1001 on tumor growth in vivo were examined in a CRPC xenograft model.

Results: GV1001 inhibited cell viability and induced apoptosis in CRPC cells in vitro, accompanied by down-regulation of Bcl-2 and caspase-3. GV1001 also inhibited different steps of angiogenesis, such as migration, invasion, and endothelial tube formation, along with decreased expression of MMP-2, MMP-9, and CD31 and increased expression of TIMP-1 and TIMP-2. Mechanistically, GV1001 significantly decreased the levels of phosphorylated AKT, phosphorylated p65, and VEGF in CRPC cells in a dose-dependent manner. GV1001 was effective in suppressing tumor growth and inducing apoptosis in a CRPC xenograft mouse model.

Conclusions: Our data demonstrated that GV1001 inhibited cell viability, induced apoptosis, and inhibited angiogenesis in CRPC cells by inhibition of the AKT/NF-κB/VEGF signaling pathway.

Keywords: castration-resistant prostate cancer, GV1001, AKT/NF-κB/VEGF signaling pathway