He Dalin, Nan Xunyi, Chang Kun-Song, Wang Yafeng, Chung Leland W K
Department of Urology, First Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Chin Med J (Engl). 2003 Sep;116(9):1394-8.
To examine the anti-oncogenic effects of promyelocytic leukemia (PML) on bladder cancer and to explore its molecular mechanisms of growth suppression.
Wild-type PML was transfected into bladder cancer cells (5637 cell) and expressed in a replication-deficient adenovirus-mediated gene delivery system and introduced into human bladder cancer cells (5637 cell) in vitro and in vivo. The effect and mechanisms of the PML gene in cell growth, clonogenicity, and tumorigenicity of bladder cancer cells were studied using in vitro and in vivo growth assays, soft agar colony-forming assay, cell cycle analysis, apoptosis assay and in vivo tumorigenicity assay.
Overexpression of PML in 5637 cells significantly reduced their growth rate and clonogenicity on soft agar. PML suppressed bladder cancer cell growth by inducing G1 cell cycle arrest and apoptosis. Adenovirus-mediated PML (Ad-PML) significantly suppressed the tumorigenicity and growth of bladder cancer cells. Intratumoral injection of Ad-PML into tumors induced by 5637 cells dramatically suppressed their growth.
The results indicated that overexpression of PML protein may promote efficient growth inhibition of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis, and adenovirus-mediated PML (Ad-PML) expression efficiently suppresses human bladder cancer growth.
研究早幼粒细胞白血病(PML)对膀胱癌的抗癌作用,并探讨其生长抑制的分子机制。
将野生型PML转染至膀胱癌细胞(5637细胞),并在复制缺陷型腺病毒介导的基因传递系统中表达,然后在体外和体内导入人膀胱癌细胞(5637细胞)。使用体外和体内生长试验、软琼脂集落形成试验、细胞周期分析、凋亡试验和体内致瘤性试验,研究PML基因对膀胱癌细胞生长、克隆形成能力和致瘤性的影响及机制。
5637细胞中PML的过表达显著降低了其生长速率和在软琼脂上的克隆形成能力。PML通过诱导G1期细胞周期停滞和凋亡来抑制膀胱癌细胞生长。腺病毒介导的PML(Ad-PML)显著抑制了膀胱癌细胞的致瘤性和生长。向由5637细胞诱导形成的肿瘤内注射Ad-PML可显著抑制其生长。
结果表明,PML蛋白的过表达可能通过诱导G1期细胞周期停滞和凋亡来促进对人膀胱癌细胞的有效生长抑制,并且腺病毒介导的PML(Ad-PML)表达可有效抑制人膀胱癌生长。