Adeno-associated virus-mediated survivin mutant Thr34Ala cooperates with oxaliplatin to inhibit tumor growth and angiogenesis in colon cancer

腺相关病毒介导的Survivin突变体Thr34Ala协同奥沙利铂抑制结肠癌肿瘤生长和血管生成

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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.

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