脂質體Tie-2-siRNA表達載體對HepG2細胞裸鼠移植瘤作用的研究_《中國普外基礎與臨床雜志》

作者：

鄧偉 ¹ , 梁力建 ²

1.廣西中醫學院附屬第一醫院肝膽外科（南寧530023）;;
2.中山大學附屬第一醫院肝膽外科（廣州510080）;

關鍵詞：

Tie-2小干擾RNA 肝癌基因治療

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目的　探討Tie-2小干擾RNA（siRNA）對HepG2細胞裸鼠皮下移植瘤的作用。
方法　將HepG2腫瘤細胞植于6周齡鼠后背皮下，荷瘤鼠分為對照組及實驗組，分別用生理鹽水/脂質體及Tie-2-siRNA/脂質體瘤內注射，檢測基因治療前后腫瘤體積、質量變化，血清AFP、MVD及腫瘤組織學變化。
結果　治療組治療后第4、7及10 d,抑瘤率分別為26.94%、53.01%及68.91%; 腫瘤體積分別為118.47、111.57 及104.59 mm3,明顯小于對照組的162.17、237.46及336.41 mm3，差異有統計學意義（P＜0.01）。腫瘤瘤重治療組輕于對照組〔（0.89±0.09） g vs （1.24±0.03） g， P＜0.01〕； AFP值治療組明顯小于對照組〔（107.66±24.13） ng/ml vs （266.08±50.96） ng/ml， P＜0.01〕; MVD值治療組亦明顯小于對照組（34.63±4.07 vs 81.01±9.44，P＜0.01）。病理組織學顯示，對照組腫瘤體積大，異形明顯；治療組可見腫瘤以壞死為主要病理改變，有大片壞死灶。治療組只有2例在壞死灶與未壞死灶腫瘤間可見凋亡細胞。
結論　Tie-2-siRNA可抑制腫瘤生長和腫瘤血管生成，為肝癌的基因治療開辟了新的思路。

引用本文： 鄧偉,梁力建. 脂質體Tie-2-siRNA表達載體對HepG2細胞裸鼠移植瘤作用的研究. 中國普外基礎與臨床雜志, 2007, 14(5): 543-546. doi: 復制

1.	Sato TN, Tozawa Y, Deutsch U, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation [Ｊ]. Nature, 1995; 376(6535)∶70.
2.	Peters KG, Coogan A, Berry D, et al. Expression of Tie2/Tek in breast tumour vasculature provides a new marker for evaluation of tumour angiogenesis [Ｊ]. Br J Cancer, 1998; 77(1)∶51.
3.	Siemeister G, Schirner M, Weindel K, et al. Two independent mechanisms essential for tumor angiogenesis: inhibition of human melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway [Ｊ]. Cancer Res， 1999; 59(13)∶3185.
4.	Wassenegger M. Gene silencing [Ｊ]. Int Rev Cytol， 2002; 219∶61.
5.	Osieka R, Houchens DP, Goldin A, et al. Chemotherapy of human colon cancer xenograft in athymic nude mice [Ｊ]. Cancer, 1977; 40(5 Suppl)∶2640.
6.	Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis [Ｊ]. Science, 1997; 277(5322)∶55.
7.	Chin KF, Greenman J, Reusch P, et al. Vascular endothelial growth factor and soluble Tie-2 receptor in colorectal cancer: associations with disease recurrence [Ｊ]. Eur J Surg Oncol, 2003; 29(6)∶497.
8.	Quartarone E, Alonci A, Allegra A, et al. Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies [Ｊ]. Eur J Haematol, 2006; 77(6)∶480.
9.	Homer JJ, Greenman J, Drevs J, et al. Soluble Tie-2 receptor levels independently predict locoregional recurrence in head and neck squamous cell carcinoma [Ｊ]. Head Neck, 2002; 24(8)∶773.
10.	鄧偉, 梁力建. 血管生成素和VEGF在人肝細胞癌血管生成作用機制的研究 [Ｊ]. 中國普通外科雜志, 2005; 14(6)∶343.
11.	Niu Q, Perruzzi C, Voskas D, et al. Inhibition of Tie-2 signaling induces endothelial cell apoptosis, decreases Akt signaling, and induces endothelial cell expression of the endogenous anti-angiogenic molecule, thrombospondin-1 [Ｊ]. Cancer Biol Ther, 2004; 3(4)∶402.
12.	Hodous BL, Geuns-Meyer SD, Hughes PE, et al. Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor [Ｊ]. J Med Chem, 2007; 50(4)∶611.
13.	Luo Y, Wen YJ, Ding ZY, et al. Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2 [Ｊ]. Clin Cancer Res, 2006; 12(6)∶1813.
14.	Popkov M, Jendreyko N, McGavern DB, et al. Targeting tu-mor angiogenesis with adenovirus-delivered anti-Tie-2 intrabody [Ｊ]. Cancer Res, 2005; 65(3)∶972.
15.	Miyazaki Y, Tang J, Maeda Y, et al. Orally active 4-amino-5-diarylurea-furo (2,3-d) pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2 [Ｊ]. Bioorg Med Chem Lett, 2007; 17(6)∶1773.
16.	Sun HC, Tang ZY, Li XM, et al. Microvessel density of hepatocellular carcinoma: its relationship with prognosis [Ｊ]. J Cancer Res Clin Oncol, 1999; 125(7)∶419.

1. 　Sato TN, Tozawa Y, Deutsch U, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation [Ｊ]. Nature, 1995; 376(6535)∶70.
2. 　Peters KG, Coogan A, Berry D, et al. Expression of Tie2/Tek in breast tumour vasculature provides a new marker for evaluation of tumour angiogenesis [Ｊ]. Br J Cancer, 1998; 77(1)∶51.
3. 　Siemeister G, Schirner M, Weindel K, et al. Two independent mechanisms essential for tumor angiogenesis: inhibition of human melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway [Ｊ]. Cancer Res， 1999; 59(13)∶3185.
4. 　Wassenegger M. Gene silencing [Ｊ]. Int Rev Cytol， 2002; 219∶61.
5. 　Osieka R, Houchens DP, Goldin A, et al. Chemotherapy of human colon cancer xenograft in athymic nude mice [Ｊ]. Cancer, 1977; 40(5 Suppl)∶2640.
6. 　Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis [Ｊ]. Science, 1997; 277(5322)∶55.
7. 　Chin KF, Greenman J, Reusch P, et al. Vascular endothelial growth factor and soluble Tie-2 receptor in colorectal cancer: associations with disease recurrence [Ｊ]. Eur J Surg Oncol, 2003; 29(6)∶497.
8. 　Quartarone E, Alonci A, Allegra A, et al. Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies [Ｊ]. Eur J Haematol, 2006; 77(6)∶480.
9. 　Homer JJ, Greenman J, Drevs J, et al. Soluble Tie-2 receptor levels independently predict locoregional recurrence in head and neck squamous cell carcinoma [Ｊ]. Head Neck, 2002; 24(8)∶773.
10. 　鄧偉, 梁力建. 血管生成素和VEGF在人肝細胞癌血管生成作用機制的研究 [Ｊ]. 中國普通外科雜志, 2005; 14(6)∶343.
11. 　Niu Q, Perruzzi C, Voskas D, et al. Inhibition of Tie-2 signaling induces endothelial cell apoptosis, decreases Akt signaling, and induces endothelial cell expression of the endogenous anti-angiogenic molecule, thrombospondin-1 [Ｊ]. Cancer Biol Ther, 2004; 3(4)∶402.
12. 　Hodous BL, Geuns-Meyer SD, Hughes PE, et al. Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor [Ｊ]. J Med Chem, 2007; 50(4)∶611.
13. 　Luo Y, Wen YJ, Ding ZY, et al. Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2 [Ｊ]. Clin Cancer Res, 2006; 12(6)∶1813.
14. 　Popkov M, Jendreyko N, McGavern DB, et al. Targeting tu-mor angiogenesis with adenovirus-delivered anti-Tie-2 intrabody [Ｊ]. Cancer Res, 2005; 65(3)∶972.
15. 　Miyazaki Y, Tang J, Maeda Y, et al. Orally active 4-amino-5-diarylurea-furo (2,3-d) pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2 [Ｊ]. Bioorg Med Chem Lett, 2007; 17(6)∶1773.
16. 　Sun HC, Tang ZY, Li XM, et al. Microvessel density of hepatocellular carcinoma: its relationship with prognosis [Ｊ]. J Cancer Res Clin Oncol, 1999; 125(7)∶419.

《中國普外基礎與臨床雜志》

脂質體Tie-2-siRNA表達載體對HepG2細胞裸鼠移植瘤作用的研究

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《中國普外基礎與臨床雜志》

脂質體Tie-2-siRNA表達載體對HepG2細胞裸鼠移植瘤作用的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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