Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle.
Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and western blotting was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5-2.0 fold enhancement in growth inhibition when compared to x-rays alone. Comparing the cell cycle change, Glu-GNPs induced acceleration in the G0/G1 phase and accumulation of cells in the G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and cyclin A, and increased expression of cyclin B1 and cyclin E. In conclusion, Glu-GNPs trigger activation of the CDK kinases leading to cell cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This activation is accompanied by a striking sensitization to ionizing radiation, which may have clinical implications.
Roa
Wilson
W
Department of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada. wilsonro@cancerboard.ab.ca
Zhang
Xiaojing
X
Guo
Linghong
L
Shaw
Andrew
A
Hu
Xiuying
X
Xiong
Yeping
Y
Gulavita
Sunil
S
Patel
Samir
S
Sun
Xuejun
X
Chen
Jie
J
Moore
Ronald
R
Xing
James Z
JZ
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D005947:Glucose / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*
D006046:Gold; D005947:Glucose