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Effectiveness of tissue specific CD/5-FC thermochemotherapy system in treatment of liver metastasis of colon cancer in nude mice
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Abstract:
Objective:To investigate the effectiveness of tissue specific cytisine deaminase/5fluorocytosine (CD/5FC) thermochemotherapy system in treatment of liver metastasis of colon cancer in nude mice. Methods: CEA promoterregulated recombinant retroviral vector G1CEACDNa was packaged, propagated and purified, and the viral supernatant was harvested. Human colon cancer LoVo cells were injected into the portal veins of 45 nude mice. Two days after the establishment of liver metastasis model, the viral supernatant was intraperitoneally injected into mice（0.2 ml/d, 5 d）. The 45 mice were then randomly divided into 3 groups, namely, the control group (injected with sodium), chemotherapy group (prodrug/5FC) and thermochemotherapy group (43 ℃ prodrug/5FC). After treated for 21 d, the mice were sacrificed and liver metastasis rate and liver metastasis nodule numbers were observed. Expression of CD gene in liver metastasis tissues was determined by RTPCR. Pathological changes of liver metastasis tissues were examined by light microscope and electron microscope.Results: The virus titer of G1CEACDNa was 5.6×106 CFU/L. CD gene was effectively expressed in the liver metastasis tissues. Liver metastasis rates and number of liver metastasis nodules were significantly lower in the thermochemotherapy group than in the chemotherapy group (13.3% vs 400%, \[0.20±0.56\] vs \[0.80±1.01\]; all P<0.05). The tumor cells grew well in the control group, and were greatly inhibited in the thermochemotherapy group compared that in the other two groups. The tumor cells showed different degrees of apoptosis in the thermochemotherapy and chemotherapy groups under electron microscope.Conclusion: The tissue specific CD/5FC thermochemotherapy system can inhibit the growth of liver metastasis of colon cancer in nude mice.
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Project Supported:
Supported by the Natural Science Foundation of Fujian Province (No.C0410045)
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