Bcl-xL DNAzymes 通过增强细胞凋亡促进结直肠癌细胞的放射敏感性和化疗敏感性。
Bcl-xL DNAzymes promote radiosensitivity and chemosensitivity in colorectal cancer cells via enhancing apoptosis.
机构信息
Department of Gastrointestinal Surgery, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830010, P. R. China.
Department of Institute for Cancer Research, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830010, P. R. China.
出版信息
BMC Pharmacol Toxicol. 2022 Feb 5;23(1):13. doi: 10.1186/s40360-022-00553-x.
BACKGROUND
RNA-cleaving deoxyribozymes (DNAzymes) are catalytic deoxyribonucleic acid molecules that have become a promising new class of gene suppressors by binding and cleaving target mRNA. This study investigated whether DNAzymes targeting Bcl-xL enhanced the effectiveness of radiotherapy and chemotherapy in colorectal cancer (CRC) cells.
METHODS
Two types of CRC cells, SW480 and SW837, were transfected with five DNAzymes. Cell viability, Bcl-xL expression and apoptosis were examined. SW480 xenograft model was used to examine the combined effects of Bcl-xL DNAzymes and 5-FU (or X-rays) on tumor growth.
RESULTS
Three Bcl-xL DNAzymes, DT882, DT883, and DT884 were identified to be effective in suppressing Bcl-xL expression and causing cell apoptosis. Furthermore, DT882 combined with 5-FU or radiotherapy addictively promoted cell apoptosis and significantly inhibited the growth of SW480 xenografts in vivo.
CONCLUSIONS
These results suggest that Bcl-xL DNAzymes can enhance the radiosensitivity and chemosensitivity in CRC cells via inducing apoptosis.
背景
RNA 切割脱氧核酶（DNAzyme）是一种结合并切割靶 mRNA 的催化脱氧核酸分子，已成为一种有前途的新型基因抑制剂。本研究探讨了针对 Bcl-xL 的 DNAzyme 是否能增强结直肠癌（CRC）细胞放化疗的疗效。
方法
用五种 DNAzyme 转染两种类型的 CRC 细胞 SW480 和 SW837。检测细胞活力、Bcl-xL 表达和细胞凋亡。建立 SW480 异种移植模型，研究 Bcl-xL DNAzyme 和 5-FU（或 X 射线）联合对肿瘤生长的影响。
结果
鉴定出三种 Bcl-xL DNAzyme（DT882、DT883 和 DT884）能有效抑制 Bcl-xL 表达并诱导细胞凋亡。此外，DT882 与 5-FU 或放疗联合可协同促进细胞凋亡，并显著抑制体内 SW480 异种移植瘤的生长。
结论
这些结果表明，Bcl-xL DNAzyme 可通过诱导细胞凋亡增强 CRC 细胞对放化疗的敏感性。
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