Synergistic antitumor effects of CDK inhibitor SNS-032 and an oncolytic adenovirus co-expressing TRAIL and Smac in pancreatic cancer

• DOI: 10.3892/mmr.2017.6472
• Publication Date: 2017-04-12T11:20:14Z
• Authors: Yun Ge; Wen Lei; Yingyu Ma; Yigang Wang; Buyun Wei; Xiaoyi Chen; Guoqing Ru; Xianglei He; Xiaozhou Mou; Shibing Wang
• Keywords: Oncolytic adenovirus; XIAP

Gene therapy using oncolytic adenoviruses is a novel approach for human cancer therapeutics. The current study aimed to investigate whether the combined use of an adenovirus expressing tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) and second mitochondria‑derived activator caspase (Smac) upon activation (ZD55‑TRAIL‑IETD‑Smac) cyclin‑dependent kinase (CDK) inhibitor SNS‑032 will synergistically reinforce their anti‑pancreatic activities. experiments in vitro demonstrated that enhances ZD55‑TRAIL‑IETD‑Smac‑induced apoptosis causes marked pancreatic cell death. Western blot assays suggested intensified cells by affecting anti‑apoptotic signaling elements, including CDK‑2, CDK‑9, Mcl‑1 XIAP. Additionally, animal further confirmed combination ZD55‑TRAIL‑IETD‑Smac significantly inhibited growth BxPC‑3 xenografts. In conclusion, present sensitizes death vivo. These findings indicate treatment with could represent rational therapy.