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

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.