Yun Chul Won, Yun Seungpil, Lee Jun Hee, Han Yong-Seok, Yoon Yeo Min, An Daniel, Lee Sang Hun
Medical Science Research Institute, Soonchunhyang University, Seoul Hospital, Seoul, Republic of Korea Department of Medical Bioscience, Soonchunhyang University, Asan, Republic of Korea.
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
Anticancer Res. 2016 Sep;36(9):4449-58. doi: 10.21873/anticanres.10989.
The putative functions of the cellular prion protein (PrP(c)) are believed to be associated with cell signaling, differentiation, survival, and cancer progression. With respect to cancer development and progression, elevations and mutations of PrP(c) expression have been shown to increase the risk for malignancy and metastasis in breast and colorectal cancer. Since both natural supplements and direct regulation of PrP(c) expression contribute to inhibition of cancer progression and growth, we hypothesized that knockdown of PrP(c) could lead to an enhanced synergic effect on the inhibition of cancer growth by fucoidan.
PrP(c) expression was suppressed in HT29 human colon cancer cells by utilizing small-interfering RNA (si-PRNP), and cells were subsequently used to study the antiproliferative and anticancer effects of fucoidan treatment of HT29 human colon cancer cells.
Fucoidan treatment significantly inhibited growth and reduced cyclin and cyclin-dependent kinase (CDK) expression in HT29 colon cancer cells. Furthermore, silencing PrP(c) expression with si-PRNP amplified the fucoidan-induced changes in cell proliferation, apoptosis, and migration. Intraperitoneal injection of si-PRNP with fucoidan reduced proliferation and tumor volume in Balb/c nude mice. This enhanced antitumor efficacy was associated with decreased angiogenesis.
Combination of fucoidan with silencing of PrP(c) has a synergic effect on the inhibition of HT29 colon cancer cell growth. Furthermore, we provide evidence for the therapeutic application of PrP(c) silencing with other anticancer drugs for cancer.
细胞朊蛋白（PrP(c)）的假定功能被认为与细胞信号传导、分化、存活及癌症进展相关。关于癌症的发生和发展，已表明PrP(c)表达的升高和突变会增加乳腺癌和结直肠癌发生恶性肿瘤及转移的风险。由于天然补充剂和对PrP(c)表达的直接调节均有助于抑制癌症进展和生长，我们推测敲低PrP(c)可能会增强岩藻依聚糖对癌症生长的抑制协同效应。
利用小干扰RNA（si-PRNP）抑制HT29人结肠癌细胞中的PrP(c)表达，随后用这些细胞研究岩藻依聚糖处理HT29人结肠癌细胞的抗增殖和抗癌作用。
岩藻依聚糖处理显著抑制HT29结肠癌细胞的生长，并降低细胞周期蛋白和细胞周期蛋白依赖性激酶（CDK）的表达。此外，用si-PRNP沉默PrP(c)表达放大了岩藻依聚糖诱导的细胞增殖、凋亡及迁移变化。腹腔注射si-PRNP与岩藻依聚糖可降低Balb/c裸鼠的肿瘤增殖和肿瘤体积。这种增强的抗肿瘤功效与血管生成减少有关。
岩藻依聚糖与PrP(c)沉默联合使用对抑制HT29结肠癌细胞生长具有协同效应。此外，我们为PrP(c)沉默与其他抗癌药物联合用于癌症治疗提供了证据。
