Study On Oncolytic Adenovirus Mediated Pinellia Pedatisecta Agglutinin

Cancer as a serious threat to human life and health, claimed millions of lives annually, whereas the traditional methods of treatment have emerged bottleneck effect. As the development of the tumor gene therapy and viral therapy, targeting gene-virotherapy has emerged, bringing new prospects for cancer treatment. We aim to selectively kill tumor cells by therapeutic genes carried by oncolytic virus vector and effective modification of the vector, and therapeutic genes and selectivity is the point.It is key to choose an excellent therapeutic gene for the new constructed adenovirus vector. In this study we choose Pinellia Pedatisecta Agglutinin (abbreviated as PPA) gene. Pinellia Pedatisecta total protein has already been shown to have anti-tumor effect. PPA was got by purification of Pinellia Pedatisecta total protein. Through the coagulation experiments it was found to be phytohemagglutinin specially combined with mannose, and it's to be believed that it is active. It was reported that expression of PPA in cells can induce apoptosis and kill tumor cells by the way that PPA could enter into the nucleus and cause chromatin condensation to form heterochromatin. A major factor in difficulty of cancer treatment is that tumor transfer easily while the glycoprotein is closely related with this, so the choice of PPA gene as a therapeutic gene can play a dual role.Modified oncolytic adenoviruses are one of the most promising vectors for gene therapy. Due to the low tumor-specific ability, the traditional adenoviruses generally have poor therapeutic efficacy and remarkable side-effect on normal cells. To further modify oncolytic adenovirus, on the basis of ZD55 we constructed the oncolytic adenoviruse using tumor-specific promoter surviving promoter (abbreviated as sp or surp) controlling exogenous gene - Pinellia Pedatisecta Agglutinin gene. Therefore, Ad-E1B(â–³55)-Surp-PPA has been constructed, it targets tumor cell only with higher security comparing with the traditional oncolytic adenovirus. In this study, Ad-E1B_(â–³55)-Surp-PPA was constructed successfully. The Ad-E1B_(â–³55)-Surp-PPA has excellent antitumor effect in vitro for human nasopharyngeal, lung, cervical carcinoma cell lines and PPA protein was expressed. Further study showed that Ad-E1B_(â–³55)-Surp-PPA induced activation of Caspase-3 and finally led to apoptosis.In conclusion, gene-virotherapy is better than gene therapy or virotherapy. The Ad-E1B_(â–³55)-Surp-PPA may be a potent anticancer agent in the clinical trials.