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Antitumor and hypoxia regulatory effect of HIF1α specific siRNA in transplanted VX2 tumor
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Abstract:
Objective:To explore the antitumor and hypoxia regulatory effect of HIF1α siRNA in tumor tissues. Methods:The HIF1α siRNA adenovirus vectors targeting HIF1α were constructed and the rabbit VX2 tumor model was established. The constructed vectors were injected into rabbits through ear vein; noninterference sequence was injected as control. PET (positron emission computed tomography) was used to observe the changes of hypoxia and necrosis in tumor tissues. The tumors were removed and the tumor volumes were measured. HE staining was used to observe the degree of the necrosis; RTPCR was used to detect the change of HIF1α expression in tumor tissues. Results: The recombinant HIF1α siRNA adenovirus vectors were successfully constructed, with a titre of 1.1×1010 pfu/mL. PET imaging showed that the SUV of 18FFDG was significantly decreased in HIF1α siRNA injected group than that in the control group (\[351±0.36\]％ vs \[8.73±0.83\]％, P<0.01). Images showed that the tumor tissue had obvious hypoxia and necrosis. The sizes of the tumors of HIF1α siRNA injected group were significantly smaller than that of the control group (P<0.01); the necrosis areas in the tumors of HIF1α siRNA injected group were significantly larger than that of control group (P<0.01). RTPCR demonstrated that the expression of HIF1α mRNA in HIF1α siRNA injected group was significantly lower than that in the control group (P<0.01). Conclusion: HIF1α specific siRNA can reduce HIF1α expression in tumor tissues and aggregate the hypoxia and necrosis of tumor tissue, therefore producing obvious antitumor effect.
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Project Supported:
Suppording by the Doctoral Research Foundation from Science and Technology Commission of Shandong Province（No. 2006BS03035）
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