title: Adeno-associated virus-mediated survivin mutant Thr34Ala cooperates with oxaliplatin to inhibit tumor growth and angiogenesis in colon cancer.
abstract: Colon cancer is one of the most common cancers. Survivin is overexpressed in human colon cancer and correlate with chemoresistance, angiogenesis and poor prognosis. Oxaliplatin, a platinum derivative cancer drug, has been used for treating human colorectal cancers. In the present study, we investigated the effect of the adeno-associated virus (AAV)-mediated survivin mutant Thr34Ala [rAAV-Sur-Mut(T34A)] on colon cancer growth. Infection with rAAV-Sur-Mut(T34A) inhibited cell proliferation, induced apoptosis and mitotic catastrophe, and sensitized colon cancer cells to chemotherapeutic drugs in vitro. Treatment with rAAV-Sur-Mut(T34A) significantly induced apoptosis, reduced angiogenesis and inhibited colon cancer growth in vivo. More importantly, rAAV-Sur-Mut(T34A) treatment strongly enhanced the anti-tumor activity of oxaliplatin and prolonged animal survival. Thus, the use of rAAV-Sur-Mut(T34A) in combination with chemotherapy may be a promising strategy for colon cancer therapy.
authors.affiliation: Laboratory Animal Center of Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou 215123, PR China.
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Xue
authors.forename: Ping Hu
authors.initials: PH
authors.lastname: Sun
authors.forename: Li Ming
authors.initials: LM
authors.lastname: Zhu
authors.forename: Shi Hu
authors.initials: SH
authors.lastname: Jiang
authors.forename: Min Min
authors.initials: MM
authors.lastname: Qiao
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Chi
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Tu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000473:pathology* / Q000517:prevention & control; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000077022:Survivin; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077022:Survivin; D000077150:Oxaliplatin