靶向survivin的反義寡核苷酸聯合三苯氧胺治療乳腺癌的研究_《中國普外基礎與臨床雜志》

作者：

宋文哲 ¹ , 宋燕 ² , 譚巖 ³ , 方艷秋 ³

1.徐州醫學院附屬醫院普通外科(江蘇徐州 221002);;
2.吉林大學中日聯誼醫院基本外科(長春 130033);;
3.吉林大學第一醫院中心研究室(長春 130021);

關鍵詞：

乳腺癌三苯氧胺 Survivin 反義寡核苷酸 Caspase-3

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目的研究聯合應用靶向survivin的反義寡核苷酸(ASODN)和三苯氧胺(TAM)對MCF-7乳腺癌細胞的作用。
方法將一條20 mer的ASODN序列與TAM作用于MCF-7乳腺癌細胞，分別為TAM組（單獨應用TAM）、ASODN組（單獨應用ASODN）及TAM+ASOND聯合組（聯合應用TAM+ASODN）。運用四甲基偶氮唑鹽比色試驗（MTT）、流式細胞儀（FCM）、原位雜交以及分光光度法分別檢測各組MCF-7細胞的抑制率、細胞周期和凋亡率、survivin mRNA表達和caspase-3活性。
結果 TAM+ASOND聯合組對MCF-7細胞的抑制率〔(62.26±3.92)%〕明顯高于TAM組〔(42.30±6.63)%〕及ASODN組〔(54.77±9.99)%〕，P lt;0.05。TAM+ASOND聯合組的細胞凋亡率為（28.08±4.32）%，明顯高于TAM組〔(18.94±4.01)%〕及ASODN組〔(21.12±3.95)%〕，P lt;0.01。TAM+ASODN聯合組對MCF-7細胞的G0/G1期阻滯作用明顯強于TAM組和ASODN組（P lt;0.05，P lt;0.01）; TAM+ASODN聯合組survivin mRNA表達陽性率為（13.38±3.45）%，明顯低于TAM組〔(39.67±7.42)%〕或ASODN組〔(27.50±5.80)%〕，P lt;0.01。 TAM+ASOND聯合組MCF-7細胞的caspase-3活性(0.93±0.13)高于TAM組(0.50±0.09)或ASODN組(0.64±0.08)，P lt;0.01。
結論靶向survivin的反義寡核苷酸能夠促進MCF-7乳腺癌細胞凋亡，增加其對TAM治療的敏感性。

引用本文： 宋文哲,宋燕,譚巖,方艷秋. 靶向survivin的反義寡核苷酸聯合三苯氧胺治療乳腺癌的研究. 中國普外基礎與臨床雜志, 2010, 17(9): 922-926. doi: 復制

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2.	謝貽祥, 孟剛. survivin在乳腺癌中的表達及其意義 [J]. 中國普外基礎與臨床雜志, 2007; 14(3): 263264.
3.	Ansell SM, Arendt BK, Grote DM, et al. Inhibition of survivin expression suppresses the growth of aggressive nonHodgkin’s lymphoma [J]. Leukemia, 2004; 18(3): 616623.
4.	馮立民, 姜希宏, 烏新林, 等. survivin反義寡核苷酸（ASODN）誘導膽囊癌細胞凋亡的研究 [J]. 中國普外基礎與臨床雜志, 2006; 13(3): 298301.
5.	陳曦海, 張豈凡, 馬榮. 反義survivin誘導胃癌SGC7901細胞凋亡及逆轉耐藥的研究 [J]. 中國普外基礎與臨床雜志, 2007; 14(1): 6367.
6.	Song X, Wang JB, Yin DL, et al. Downregulation of lung resistance related protein by RNA interference targeting survivin induces the reversal of chemoresistances in hepatocellular carcinoma [J]. Chin Med J (Engl), 2009; 122(21): 26362642.
7.	Zaffaroni N, Pennati M, Collella G, et al. Expression of the antiapoptotic gene survivin correlates with taxol resistance in human ovarian cancer [J]. Cell Mol Life Sci, 2002; 59(8): 14061412.
8.	Olie RA, SimesWüst AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy [J]. Cancer Res, 2000; 60(11): 28052809.
9.	Ryan BM, O’Donovan N, Duffy MJ. Survivin: a new target for anticancer therapy [J]. Cancer Treat Rev, 2009; 35(7): 553562.
10.	Dai DJ, Lu CD, Lai RY, et al. Survivin antisense compound inhibits proliferation and promotes apoptosis in liver cancer cells [J]. World J Gastroenterol, 2005; 11(2): 193199.
11.	孫艷, 李勇, 范立僑, 等. survivin反義寡核苷酸對人卵巢癌細胞株中survivin和SMAC/DIABLO基因表達的影響 [J]. 南方醫科大學學報, 2007; 27(10): 15711574.
12.	Mita AC, Mita MM, Nawrocki ST, et al. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics [J]. Clin Cancer Res, 2008; 14(16): 50005005.
13.	Yamamoto H, Ngan CY, Monden M. Cancer cells survive with survivin [J]. Cancer Sci, 2008; 99(9): 17091714.
14.	Bendardaf R, Ristamaki R, Syrjanen K, et al. Bcl2 expression significantly correlates with thymidylate synthase expression in colorectal cancer patients [J]. World J Gastroenterol, 2008; 14(40): 62186223.
15.	Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl2 family [J]. J Cell Sci, 2009; 122(Pt 4): 437441.
16.	Kang MH, Reynolds CP. Bcl2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy [J]. Clin Cancer Res, 2009; 15(4): 11261132.
17.	Spender LC, Inman GJ. Targeting the BCL2 family in malignancies of germinal centre origin [J]. Expert Opin Ther Targets, 2009; 13(12): 14591472.
18.	Patel MP, Masood A, Patel PS, et al. Targeting the Bcl2 [J]. Curr Opin Oncol, 2009; 21(6): 516523.
19.	Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin [J]. Nature, 1998; 396(6711): 580584.
20.	Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16IN K4a and Cdk2/cyclin E complex activation [J]. Oncogene, 2000; 19(29): 32253234.
21.	戴德堅, 吳丹, 孟化, 等. 反義survivin脂質體復合物對肝癌細胞生長凋亡和細胞周期的影響 [J]. 中華腫瘤雜志, 2005; 27(10): 581585.
22.	Pradelli LA, Bénéteau M, Ricci JE. Mitochondrial control of caspasedependent and independent cell death [J]. Cell Mol Life Sci, 2010; 67(10): 15891597.
23.	Tamm I, Wang Y, Sausville E, et al. IAPfamily protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs [J]. Cancer Res, 1998; 58(23): 53155320.
24.	Li YH, Wang C, Meng K, et al. Influence of survivin and caspase3 on cell apoptosis and prognosis in gastric carcinoma [J]. World J Gastroenterol, 2004; 10(13): 19841988.
25.	Wang JX, Zheng S. Caspase3 and survivin expression in pediatric neuroblastoma and their roles in apoptosis [J]. Chin Med J (Engl), 2004; 117(12): 18211824.

1. Ambrosini G, Adida C, Altieri DC. A novel antiapoptosis gene, survivin, expressed in cancer and lymphoma [J]. Nat Med, 1997; 3(8): 917921.
2. 謝貽祥, 孟剛. survivin在乳腺癌中的表達及其意義 [J]. 中國普外基礎與臨床雜志, 2007; 14(3): 263264.
3. Ansell SM, Arendt BK, Grote DM, et al. Inhibition of survivin expression suppresses the growth of aggressive nonHodgkin’s lymphoma [J]. Leukemia, 2004; 18(3): 616623.
4. 馮立民, 姜希宏, 烏新林, 等. survivin反義寡核苷酸（ASODN）誘導膽囊癌細胞凋亡的研究 [J]. 中國普外基礎與臨床雜志, 2006; 13(3): 298301.
5. 陳曦海, 張豈凡, 馬榮. 反義survivin誘導胃癌SGC7901細胞凋亡及逆轉耐藥的研究 [J]. 中國普外基礎與臨床雜志, 2007; 14(1): 6367.
6. Song X, Wang JB, Yin DL, et al. Downregulation of lung resistance related protein by RNA interference targeting survivin induces the reversal of chemoresistances in hepatocellular carcinoma [J]. Chin Med J (Engl), 2009; 122(21): 26362642.
7. Zaffaroni N, Pennati M, Collella G, et al. Expression of the antiapoptotic gene survivin correlates with taxol resistance in human ovarian cancer [J]. Cell Mol Life Sci, 2002; 59(8): 14061412.
8. Olie RA, SimesWüst AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy [J]. Cancer Res, 2000; 60(11): 28052809.
9. Ryan BM, O’Donovan N, Duffy MJ. Survivin: a new target for anticancer therapy [J]. Cancer Treat Rev, 2009; 35(7): 553562.
10. Dai DJ, Lu CD, Lai RY, et al. Survivin antisense compound inhibits proliferation and promotes apoptosis in liver cancer cells [J]. World J Gastroenterol, 2005; 11(2): 193199.
11. 孫艷, 李勇, 范立僑, 等. survivin反義寡核苷酸對人卵巢癌細胞株中survivin和SMAC/DIABLO基因表達的影響 [J]. 南方醫科大學學報, 2007; 27(10): 15711574.
12. Mita AC, Mita MM, Nawrocki ST, et al. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics [J]. Clin Cancer Res, 2008; 14(16): 50005005.
13. Yamamoto H, Ngan CY, Monden M. Cancer cells survive with survivin [J]. Cancer Sci, 2008; 99(9): 17091714.
14. Bendardaf R, Ristamaki R, Syrjanen K, et al. Bcl2 expression significantly correlates with thymidylate synthase expression in colorectal cancer patients [J]. World J Gastroenterol, 2008; 14(40): 62186223.
15. Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl2 family [J]. J Cell Sci, 2009; 122(Pt 4): 437441.
16. Kang MH, Reynolds CP. Bcl2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy [J]. Clin Cancer Res, 2009; 15(4): 11261132.
17. Spender LC, Inman GJ. Targeting the BCL2 family in malignancies of germinal centre origin [J]. Expert Opin Ther Targets, 2009; 13(12): 14591472.
18. Patel MP, Masood A, Patel PS, et al. Targeting the Bcl2 [J]. Curr Opin Oncol, 2009; 21(6): 516523.
19. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin [J]. Nature, 1998; 396(6711): 580584.
20. Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16IN K4a and Cdk2/cyclin E complex activation [J]. Oncogene, 2000; 19(29): 32253234.
21. 戴德堅, 吳丹, 孟化, 等. 反義survivin脂質體復合物對肝癌細胞生長凋亡和細胞周期的影響 [J]. 中華腫瘤雜志, 2005; 27(10): 581585.
22. Pradelli LA, Bénéteau M, Ricci JE. Mitochondrial control of caspasedependent and independent cell death [J]. Cell Mol Life Sci, 2010; 67(10): 15891597.
23. Tamm I, Wang Y, Sausville E, et al. IAPfamily protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs [J]. Cancer Res, 1998; 58(23): 53155320.
24. Li YH, Wang C, Meng K, et al. Influence of survivin and caspase3 on cell apoptosis and prognosis in gastric carcinoma [J]. World J Gastroenterol, 2004; 10(13): 19841988.
25. Wang JX, Zheng S. Caspase3 and survivin expression in pediatric neuroblastoma and their roles in apoptosis [J]. Chin Med J (Engl), 2004; 117(12): 18211824.

《中國普外基礎與臨床雜志》

靶向survivin的反義寡核苷酸聯合三苯氧胺治療乳腺癌的研究

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《中國普外基礎與臨床雜志》

靶向survivin的反義寡核苷酸聯合三苯氧胺治療乳腺癌的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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