The Treatment Of Hepatocellular Carcinoma By A Oncolytic Adenovirus Carrying A Pinellia Pedatisecta Agglutinin Gene In Vitro And In Vivo

Hepatocellular carcinoma (HCC) is one of the most prevailing malignant tumors, whichendangers people’s lives due to its high incidence and mortality. At present, the remedy focusedon traditional treatment method, and yet, it appears to be serious bottleneck. In contrast,biological remedies are expected to be the main tools for fighting against HCC, because itbehaves multiply functions: activating immune system, minimal side effects, specificities andrectifying targeting genes.Pinellia pedatisecta agglutinin (PPA) is a very common mannose-binding lectin that gathersin the tuber of P. pedatisecta. Due to its mannose-binding activity, PPA may provide a usefultool in studies of the invasion, metastasis and prognosis of tumors. Presently, plant lectins havealready been employed in systematic cancers, opening a new way to employ the developmentand diagnosis of cancer.In this work, we combine the PPA with the Cancer Targeting Gene-Viro-Therapy to studythe effects of PPA against cancers. The in vitro results showed that PPA inducedanti-proliferative effects on vavious cancer cells. In vivo studies showed that PPA inducedinfiltration of macrophages and subsequent phagocytosis of Bel-7404cells by macrophages.Method(1) Recombination oncolytic adenovirus ZD55-PPA was packaged by an Adeasy system.(2)MTT assays detected that ZD55-PPA inhibited the proliferation of cancer cells.(3) The casualtyand safety of the adenovirus was examined by a morphological study.(4) The Pathologicalchanges tested by Crystal Violet.(5) The expression of PPA was examined by RT-PCR in mRNAlevel.(6) The apoptosis of Bel-7404was inspected by Flow Cytometry.(7) The antitumor effectsof PPA reviewed in naked mice, HE stains and transmission electron microscopy.Results (1) We successful constructed ZD55-PPA by an Adeasy systerm.(2) PPA can remarkableinhibited the proliferation of the cancer cells by MTT assay, morphology and Crystal Violet,RT-PCR assay demonstrated that PPA has the much higher expression in mRNA level,Interestingly, Flow Cytometry analysis showed that the main death of cancer cells may notcaused by apoptosis, maybe by the other unknown ways.(3) The cell death was caused byrecruiting macrophage to inducing the phagocytes by Bel-7404xenograft tumor experiment.ConclusionIn vitro studies showed that ZD55-PPA elicited significant cytotoxicity against variouscancer cells. In vivo studies showed that ZD55-PPA induced obvious macrophage infiltrationand the phagocytosis of cancer cells by macrophages, instead of traditional apoptosis.