• 1.徐州醫(yī)學(xué)院附屬醫(yī)院普通外科(江蘇徐州 221002);;
  • 2.吉林大學(xué)中日聯(lián)誼醫(yī)院基本外科(長春 130033);;
  • 3.吉林大學(xué)第一醫(yī)院中心研究室(長春 130021);

目的 研究聯(lián)合應(yīng)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(xì)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(xì)胞，分別為TAM組（單獨應(yīng)用TAM）、ASODN組（單獨應(yīng)用ASODN）及TAM+ASOND聯(lián)合組（聯(lián)合應(yīng)用TAM+ASODN）。運用四甲基偶氮唑鹽比色試驗（MTT）、流式細(xì)胞儀（FCM）、原位雜交以及分光光度法分別檢測各組MCF-7細(xì)胞的抑制率、細(xì)胞周期和凋亡率、survivin mRNA表達(dá)和caspase-3活性。
結(jié)果 TAM+ASOND聯(lián)合組對MCF-7細(xì)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(lián)合組的細(xì)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(lián)合組對MCF-7細(xì)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(lián)合組survivin mRNA表達(dá)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(lián)合組MCF-7細(xì)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(jié)論 靶向survivin的反義寡核苷酸能夠促進(jìn)MCF-7乳腺癌細(xì)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(lián)合三苯氧胺治療乳腺癌的研究. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(9): 922-926. doi: 復(fù)制

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(dá)及其意義 [J]. 中國普外基礎(chǔ)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(dǎo)膽囊癌細(xì)胞凋亡的研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(3): 298301.
5. 陳曦海, 張豈凡, 馬榮. 反義survivin誘導(dǎo)胃癌SGC7901細(xì)胞凋亡及逆轉(zhuǎn)耐藥的研究 [J]. 中國普外基礎(chǔ)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(xì)胞株中survivin和SMAC/DIABLO基因表達(dá)的影響 [J]. 南方醫(yī)科大學(xué)學(xué)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(zhì)體復(fù)合物對肝癌細(xì)胞生長凋亡和細(xì)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. 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. 2. 謝貽祥, 孟剛. survivin在乳腺癌中的表達(dá)及其意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2007; 14(3): 263264.
  3. 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. 4. 馮立民, 姜希宏, 烏新林, 等. survivin反義寡核苷酸（ASODN）誘導(dǎo)膽囊癌細(xì)胞凋亡的研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(3): 298301.
  5. 5. 陳曦海, 張豈凡, 馬榮. 反義survivin誘導(dǎo)胃癌SGC7901細(xì)胞凋亡及逆轉(zhuǎn)耐藥的研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2007; 14(1): 6367.
  6. 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. 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. 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. 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. 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. 11. 孫艷, 李勇, 范立僑, 等. survivin反義寡核苷酸對人卵巢癌細(xì)胞株中survivin和SMAC/DIABLO基因表達(dá)的影響 [J]. 南方醫(yī)科大學(xué)學(xué)報, 2007; 27(10): 15711574.
  12. 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. 13. Yamamoto H, Ngan CY, Monden M. Cancer cells survive with survivin [J]. Cancer Sci, 2008; 99(9): 17091714.
  14. 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. 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. 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. 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. 18. Patel MP, Masood A, Patel PS, et al. Targeting the Bcl2 [J]. Curr Opin Oncol, 2009; 21(6): 516523.
  19. 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. 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. 21. 戴德堅, 吳丹, 孟化, 等. 反義survivin脂質(zhì)體復(fù)合物對肝癌細(xì)胞生長凋亡和細(xì)胞周期的影響 [J]. 中華腫瘤雜志, 2005; 27(10): 581585.
  22. 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. 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. 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. 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.