Efficient induction of apoptosis by ONYX-015 adenovirus in human colon cancer cell lines regardless of p53 status

被引:14
作者
Petit, T
Davidson, KK
Cerna, C
Lawrence, RA
Von Hoff, DD
Heise, C
Kirn, D
Izbicka, E
机构
[1] Canc Therapy & Res Ctr S Texas, Inst Drug Dev, Mol Targets Lab, San Antonio, TX 78245 USA
[2] Onyx Pharmaceut, Richmond, CA 94806 USA
关键词
apoptosis; ONYX-015; adenovirus; p53;
D O I
10.1097/00001813-200201000-00005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The ONYX-015 virus Is a mutated adenovirus that in theory selectively replicates and induces cytolysis in tumor cells lacking functional p53. The present study investigated whether ONYX-015 viral infection alone or in combination with conventional chemotherapeutic agents could significantly increase apoptosis in human colon cancer cell lines, regardless of p53 status, compared to untreated cells. A pair of colon cancer cell lines that differ only in their p53 status (RKO with wild-type p53 and RKOp53 with deficient p53) was tested. Two chemotherapeutic agents, 5-fluorouracil (5-FU) and CPT-11, were tested in combination with ONYX-015. Final concentrations of these agents corresponded to peak plasma levels achievable in patients. ONYX-015 concentration was 10 p.f.u./cell. In RKO and RKOp53 cell lines, ONYX-015 viral infection alone or in combination with 5-FU or CPT-11 induced a significant increase in apoptosis compared to chemotherapeutic agents alone, regardless of p53 status. Moreover, the combination of ONYX-015 and chemotherapeutics induced more apoptosis than chemotherapeutics alone in the two colon cancer cell lines Independently of their p53 status. We conclude that ONYX-015 virus infection alone or in combination with 5-FU or CPT-11 induced apoptosis in human colon cancer cell lines, independently of p53 status. [(C) 2002 Lippincott Williams Wilkins.].
引用
收藏
页码:47 / 50
页数:4
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