Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
J Gene Med. 2012 Dec;14(12):761-8. doi: 10.1002/jgm.2681.
Bcl-XL, a mitochondria membrane protein, is overexpressed in colorectal cancers and promotes cell survival. We have previously shown that the adenovector expressing small hairpin (sh)RNA targeting Bcl-XL could induce significantly apoptosis in colon cancer cells. In the present study, we aimed to further detect the anti-cancer effect of adenovector expressing the shRNA targeting Bcl-XL (Ad/Bcl-XL shRNA) on rectal cancer xenografts that were derived from patient tumors.
We first established three rectal cancer xenografts. These xenografts were subsequently treated with Ad/Bcl-XL shRNA alone or in combination with 5-fluouracil (5-Fu). Finally, the inhibition of tumor growth, survival time and induction of apoptosis were analyzed.
The results obtained demonstrated that Ad/Bcl-XL shRNA could effectively suppress the tumor growth of all three rectal cancer xenografts and prolong their survival time. After being combined with 5-Fu, the suppressing effect of Ad/Bcl-XL shRNA was enhanced further. In addition, the data also showed that Ad/Bcl-XL shRNA combined with 5-Fu could significantly increase the apoptotic ratio in the rectal cancer xenograft.
These data indicate that Ad/Bcl-XL shRNA with or without 5-Fu has effective anti-tumor effects on the patient tumor-derived rectal cancer xenografts, suggesting that it could be a potential strategy for rectal cancer therapy.
Bcl-XL 是一种位于线粒体膜上的蛋白,在结直肠癌中过度表达,并促进细胞存活。我们先前的研究表明,表达针对 Bcl-XL 的短发夹 RNA(shRNA)的腺病毒载体可显著诱导结肠癌细胞凋亡。在本研究中,我们旨在进一步检测针对 Bcl-XL 的 shRNA 表达腺病毒载体(Ad/Bcl-XL shRNA)对源自患者肿瘤的直肠癌细胞异种移植瘤的抗癌作用。
我们首先建立了三个直肠癌细胞异种移植瘤。随后,单独用 Ad/Bcl-XL shRNA 或联合氟尿嘧啶(5-Fu)对这些异种移植瘤进行处理。最后,分析肿瘤生长抑制、生存时间和诱导凋亡的情况。
结果表明,Ad/Bcl-XL shRNA 可有效抑制所有三种直肠癌细胞异种移植瘤的生长,并延长其生存时间。与 5-Fu 联合使用后,Ad/Bcl-XL shRNA 的抑制作用进一步增强。此外,数据还显示,Ad/Bcl-XL shRNA 联合 5-Fu 可显著增加直肠癌细胞异种移植瘤中的凋亡比例。
这些数据表明,Ad/Bcl-XL shRNA 联合或不联合 5-Fu 对源自患者肿瘤的直肠癌细胞异种移植瘤具有有效的抗肿瘤作用,提示其可能是直肠癌症治疗的一种潜在策略。