Synergistic Suppression Effect On Tumor Growth Of Hepatocellular Carcinoma By Combining Oncolytic Adenovirus ZD55-XAF1with Cisplatin

As most common cancer worldwide, liver cancer holds the second death rateamong all cancer, and trend of the incidence grows year after year. Genetic disorder isconsidered the main reason to be responsible for the happening of cancer, whichcauses a high light on gene therapy. Oncolytic adenovirus is known as an ideal vectorto carry anti-tumor gene into host cells due to its high efficiency of infection,unconformity and low production cost. Through further reconstruction, includingshell of adenovirus, the promoter, insert foreign genes, make the adenovirus on tumorcell has a strong targeted and the exogenous gene makes adenovirus kill cancer cellsmore efficiently. As traditional tumor therapy, chemotherapy still plays important rolein clinic, such as DDP and DOX. However, cancer cells displays high resistance toDDP and one of the major clinical obstacles in chemotherapy is severe side effects.XAF1was first isolated by the yeast two-hybrid technique on the basis of itsability to bind XIAP, thus inhibit its anti-apoptosis function. In the study, wecombined DDP with ZD55-XAF1for growth inhibition of hepatocellular carcinoma(HCC) cells. The ZD55-XAF1was constructed by depleting the E1B55KD andinserted the XAF1gene-expressing cassette. We found that the combination ofZD55-XAF1and cisplatin showed enhanced inhibitory effects on the proliferation ofHCC cells in vitro and tumor growth in mice. Furthermore, the combined treatment ofZD55-XAF1and DDP decreases the chemotherapy dose needed to achieve the sameinhibitory effect without overlapping toxicities on normal liver cells and inducestumor cell apoptosis via the activation of caspase-9/PARP pathway. Pathologicalanalysis of tumor showed that combination of ZD55-XAF1and DDP enhanceapoptosis in tumor, while existence of DDP had no influence on XAF1expression.Furthermore, HE staining analysis of liver showed ZD55-XAF1put low cytotoxicity on liver by intratumor injection.In conclusion, combination of ZD55-XAF1with DDP showed enhancedanti-tumor effect in vitro and in vivo, and enhanced apoptosis was found in carcinomacells with activation of apoptosis signaling pathway. Through this research,combination of oncolytic adenovirus and chemotherapy may provide a basis forclinical treatment of liver cancer.