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Bcl-x（L）反义寡核苷酸使结肠癌细胞对放疗敏感。

Bcl-x(L) antisense oligonucleotides radiosensitise colon cancer cells.

作者信息

Wacheck V, Selzer E, Günsberg P, Lucas T, Meyer H, Thallinger C, Monia B P, Jansen B

机构信息

Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.

出版信息

Br J Cancer. 2003 Oct 6;89(7):1352-7. doi: 10.1038/sj.bjc.6601254.

DOI:10.1038/sj.bjc.6601254
PMID:14520471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2394316/
Abstract

Advanced colon cancer is a malignancy with poor response to various treatment modalities including ionising radiation (IR) and chemotherapy. Both IR and chemotherapeutic agents have been shown to act by inducing apoptosis, a type of cell death antagonised by the Bcl-x(L) gene product. Since approximately 60% of human colon cancers express Bcl-x(L), it was the aim of this study to explore the potential of Bcl-x(L) antisense oligonucleotides as a novel radiosensitisation strategy. Caco-2 colon cancer cells were treated with Bcl-x(L) antisense oligonucleotides in combination with IR or cisplatin, and Bcl-x(L) protein expression, apoptosis, cell viability and clonogenic survival were examined. Bcl-x(L) antisense oligonucleotide specifically reduced the Bcl-x(L) protein level by almost 50% in Caco-2 cells. The decreased threshold for the induction of apoptosis resulted in a 300% increase of apoptosis after IR or cisplatin treatment and led to a 60% reduction of cell proliferation beyond response rates achieved with IR. These data suggest that Bcl-x(L) is an important factor contributing to the treatment resistance of human colon cancer. Specific reduction of Bcl-x(L) protein levels by antisense oligonucleotides qualifies as a promising therapeutic strategy for colon cancer that may help overcome resistance and improve clinical outcome in this malignancy.

摘要

晚期结肠癌是一种对包括电离辐射（IR）和化疗在内的各种治疗方式反应不佳的恶性肿瘤。IR和化疗药物均已被证明通过诱导凋亡起作用，凋亡是一种受Bcl-x(L)基因产物拮抗的细胞死亡类型。由于大约60%的人类结肠癌表达Bcl-x(L)，本研究的目的是探索Bcl-x(L)反义寡核苷酸作为一种新型放射增敏策略的潜力。用Bcl-x(L)反义寡核苷酸联合IR或顺铂处理Caco-2结肠癌细胞，并检测Bcl-x(L)蛋白表达、凋亡、细胞活力和克隆形成存活率。Bcl-x(L)反义寡核苷酸在Caco-2细胞中特异性地将Bcl-x(L)蛋白水平降低了近50%。凋亡诱导阈值的降低导致IR或顺铂处理后凋亡增加300%，并导致细胞增殖减少60%，超过了IR所达到的反应率。这些数据表明Bcl-x(L)是导致人类结肠癌治疗耐药的一个重要因素。通过反义寡核苷酸特异性降低Bcl-x(L)蛋白水平是一种有前景的结肠癌治疗策略，可能有助于克服耐药性并改善这种恶性肿瘤的临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/c4d68ea454c0/89-6601254f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/6ccafed200d5/89-6601254f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/289750be8080/89-6601254f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/85c51e316c53/89-6601254f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/4fb2ad9bcd50/89-6601254f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/c4d68ea454c0/89-6601254f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/6ccafed200d5/89-6601254f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/289750be8080/89-6601254f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/85c51e316c53/89-6601254f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/4fb2ad9bcd50/89-6601254f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4929/2394316/c4d68ea454c0/89-6601254f5.jpg

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