腫瘍溶解ウイルスとシスプラチンとの併用効果の検討

Ad-ARET

北海道歯学会

北海道歯学雑誌

The Oncolytic Adenovirus is an attractive tool for cancer therapy. We developed a new oncolytic adenovirus Ad-ARET including the AU-rich element (ARE) in the 3’-utranslated region (3’-UTR) of the E1A gene. ARE is the RNA element which enhances the rapid decay of mRNAs including those of the genes required for cell growth and proliferation. In the vast majority of cancer cells, the amount of cytoplasmic HuR, which binds to ARE and protects AREmRNA from rapid degradation. In this case ARE-mRNA is also up-regulated and stabilized. And the stabilization is corelated with the malignancy of the cancer cells. 　Cisplatin demonstrates significant anti-tumor activity against a wide variety of tumors. Since cisplatin may injure normal cells, ineffective drug treatment of cancer tissue causes some side effects. The combination of oncolytic virus and cisplatin can allow the use of a reduced dosage of each reagent, and reduce side effects. 　In this study, I examined the combination effect of Ad-ARET with cisplatin using several kinds of cancer cells. In the case of a combined use of Ad-ARET with cisplatin, the cell survival rate of cancer cells was lower compared with those of single treatments. The combined effect was also evident in cisplatin-resistant cells. I found that the cisplatin treatment induced HuR export resulting in up-regulation of Ad-ARET replication through E1A mRNA stabilization. These results indicate that Ad-ARET is possible for combination cancer therapy with cisplatin.