Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Integr Cancer Ther. 2009 Sep;8(3):261-72. doi: 10.1177/1534735409343589.
The present study was carried out to evaluate the radioprotective efficacy of Podophyllum hexandrum fraction (REC-2006) in hepatoma cell lines having different p53 statuses. Higher radioresistance was observed in the HepG2 (p53(++)) cell line in comparison to the Hep3B (p53(-)) cell line, indicating a plausible role of p53 in radioresistance. REC-2006 exhibited nearly twice the survival in p53-expressing HepG2 cells compared with p53-negative Hep3B cells. REC-2006 treatment alone induced p53 expression as compared with untreated controls. However, REC-2006 reduced p53 expression when treated 2 hours before irradiation as compared with the irradiated HepG2 controls, indicating that REC-2006 modulates the expression of p53 to mitigate its apoptotic effect. Induction of p21 in the REC-2006 + radiation treatment group downregulated the expression of cyclin E and CDK2, leading to a delay in the G1 phase of HepG2 cells, which provided time for DNA repair or related processes. However, no significant difference in CDC2 expression in both cell lines suggested that G2 phase arrest might not be the only responsible factor for REC-2006-mediated radioprotection. Significant induction of PCNA and GADD45 expression in HepG2 cells suggested that REC-2006 increased the percentage survival of HepG2 cells by increasing the span of time as well as efficacy for repair processes. In conclusion, REC-2006 modulated the expression of p53 and thereby promoted cell cycle arrest in the G1 phase, encouraging cell proliferation and DNA repair and thus providing significantly higher protection against acute gamma-radiation in the HepG2 cell line.
本研究旨在评估鬼臼类叶升麻提取物（REC-2006）在具有不同 p53 状态的肝癌细胞系中的放射防护作用。与 Hep3B（p53(-)）细胞系相比，HepG2（p53(++））细胞系表现出更高的放射抗性，表明 p53 在放射抗性中可能发挥作用。与 p53 阴性的 Hep3B 细胞相比，REC-2006 在表达 p53 的 HepG2 细胞中的存活率几乎增加了一倍。与未处理的对照相比，REC-2006 单独处理可诱导 p53 表达。然而，与照射的 HepG2 对照相比，REC-2006 在照射前 2 小时处理可降低 p53 表达，表明 REC-2006 可调节 p53 的表达以减轻其凋亡作用。在 REC-2006 + 辐射处理组中诱导 p21 下调了细胞周期蛋白 E 和 CDK2 的表达，导致 HepG2 细胞的 G1 期延迟，为 DNA 修复或相关过程提供了时间。然而，在两种细胞系中 CDC2 表达均无显著差异表明，G2 期阻滞可能不是 REC-2006 介导的放射防护的唯一负责因素。在 HepG2 细胞中 PCNA 和 GADD45 表达的显著诱导表明，REC-2006 通过增加修复过程的时间跨度和效力来提高 HepG2 细胞的存活率，从而增加了 HepG2 细胞的存活百分比。总之，REC-2006 调节了 p53 的表达，从而促进了 G1 期细胞周期阻滞，鼓励细胞增殖和 DNA 修复，从而为 HepG2 细胞系提供了显著更高的急性γ射线防护作用。
