The proteasome inhibitor bortezomib (Velcade) sensitizes some human tumor cells to Apo2L/TRAIL-mediated apoptosis

被引：34

作者：

Brooks, AD

Ramirez, T

Toh, U

Onksen, J

Elliott, PJ

Murphy, WJ

Sayers, TJ ^{[1
]}

机构：

[1] NCI, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA

[2] NCI, Expt Immunol Lab, Frederick, MD 21701 USA

[3] Kurume Univ, Dept Surg, Kurume, Fukuoka 830, Japan

[4] Combinatorex, Boston, MA USA

[5] Univ Nevada, Reno, NV USA

来源：

TUMOR PROGRESSION AND THERAPEUTIC RESISTANCE | 2005年 / 1059卷

关键词：

apoptosis; bortezomib; velcade; Apo2L/TRAIL;

D O I：

10.1196/annals.1339.042

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

On testing a panel of different human cancer cell lines, we observed that the proteasome inhibitor bortezomib could dramatically sensitize some lines to the apoptotic effects of Apo2L/TRAIL. Certain renal, colon, or breast tumor cell lines were dramatically sensitized, whereas other tumor lines from the same tissue of origin remained resistant. This sensitization did not correlate with either the p53 status of the individual tumor cell lines or their intrinsic sensitivity to Apo2L/TRAIL. Colon cancer cell lines lacking p53 or Bax were sensitized by bortezomib, suggesting that neither p53 nor Bax levels were crucial for sensitization. Although the molecular basis of bortezomib sensitization of tumor cells to Apo2L/TRAIL remains to be determined, this combination can have an enhanced apoptotic effect over either agent alone for certain human cancer cells.

引用

页码：160 / 167

页数：8

共 13 条

[1]

Adams J, 1999, CANCER RES, V59, P2615

[2] Protease inhibitor-induced apoptosis:: accumulation of wt p53, p21WAF1/CIP1 and induction of apoptosis are independent markers of proteasome inhibition [J].