• 1. 南京市高淳縣人民醫(yī)院普外科( 江蘇南京 211300);;
  • 2. 南京大學(xué)醫(yī)學(xué)院附屬鼓樓醫(yī)院肝膽外科( 江蘇南京 210008);;
  • 3. 南京大學(xué)醫(yī)學(xué)院( 江蘇南京 210008);

目的 　探討干細(xì)胞標(biāo)志物三磷酸腺苷結(jié)合盒超家族G家族第2個成員（ATP-binding cassette superfamily G member 2，ABCG2）在人肝癌細(xì)胞株中的表達(dá)及其與肝癌耐藥的關(guān)系，觀察人肝癌細(xì)胞株中ABCG2陽性表達(dá)和陰性表達(dá)細(xì)胞的功能差異。
方法 　流式細(xì)胞儀檢測ABCG2在人肝癌細(xì)胞株P(guān)LC/PRF/5、7402、7701及7721中的陽性表達(dá)，計算5-氟尿嘧啶（5-FU）、阿霉素的半數(shù)抑制濃度（IC50）值。采用免疫熒光染色觀察ABCG2在肝癌7721細(xì)胞株中的表達(dá)，并進(jìn)行無菌流式分選，觀察ABCG2陽性表達(dá)與ABCG2陰性表達(dá)的肝癌7721細(xì)胞的功能差異。
結(jié)果 　在4種肝癌細(xì)胞株中7721細(xì)胞株ABCG2表達(dá)陽性率最高（P＜0.05），且流式細(xì)胞圖中陽性表達(dá)和陰性表達(dá)細(xì)胞呈明顯雙峰。5-FU、阿霉素對7721細(xì)胞株的IC50值明顯高于其他3種細(xì)胞株，除與5-FU對7701細(xì)胞的IC50值差異無統(tǒng)計學(xué)意義（P＞0.05）外，其余比較差異均有統(tǒng)計學(xué)意義（P＜0.05）。分選后的ABCG2陽性表達(dá)細(xì)胞與陰性表達(dá)細(xì)胞的增殖差異無統(tǒng)計學(xué)意義（P＞0.05）；ABCG2陽性表達(dá)細(xì)胞較陰性表達(dá)細(xì)胞更多處于相對靜止期（P＜0.05）。
結(jié)論 　ABCG2在人多種肝癌細(xì)胞株中均表達(dá)，ABCG2表達(dá)陽性率越高的細(xì)胞較表達(dá)陽性率越低的細(xì)胞更具有耐藥性，ABCG2陽性表達(dá)細(xì)胞處于相對靜止期。

引用本文： 強(qiáng)光輝,余德才,丁希偉,江春平. ABCG2 在人肝癌細(xì)胞株中的表達(dá)及其相關(guān)功能. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(2): 146-150. doi: 復(fù)制

1. Robey RW，Polgar O，Deeken J，et al．ABCG2：determining its relevance in clinical drug resistance[J]．Cancer Metastasis Rev， 2007，26(1)：39-57．.
2. Zhou S，Schuetz JD，Bunting KD，et al．The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype[J]．Nat Med，2001，7(9)：1028-1034．.
3. Ding XW，Wu JH，Jiang CP．ABCG2：a potential marker of stem cells and novel target in stem cell and cancer therapy[J]． Life Sci，2010，86(17-18)：631-637．.
4. Ross DD，Nakanishi T．Impact of breast cancer resistance protein on cancer treatment outcomes[J]．Methods Mol Biol，2010， 596：251-290．.
5. Dean M，F(xiàn)ojo T，Bates S．Tumour stem cells and drug resistance[J]．Nat Rev Cancer，2005，5(4)：275-284．.
6. 徐叔云，卞如濂，陳修．藥理實驗方法[ M]．第 2版．北京：人民衛(wèi)生出版社，1991：731．.
7. 劉寶瑞，王婷婷，錢曉萍．原發(fā)性肝癌分子靶向治療研究進(jìn)展[ J]．世界華人消化雜志，2009，17(10)：993-997．.
8. Li F，Tiede B，Massagué J，et al．Beyond tumorigenesis：cancer stem cells in metastasis[J]．Cell Res，2007，17(1)：3-14．.
9. Visvader JE，Lindeman GJ．Cancer stem cells in solid tumours： accumulating evidence and unresolved questions[J]．Nat Rev Cancer，2008，8(10)：755-768．.
10. Chiba T，Kita K，Zheng YW，et al．Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J]．Hepatology，2006，44(1)：240-251．.
11. Kim M，Turnquist H，Jackson J，et al．The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst33342 and is overexpressed in hematopoietic stem cells[J]．Clin Cancer Res，2002，8(1)：22-28．.
12. Scharenberg CW，Harkey MA,Torok-Storb B．The ABCG2 transporter is an efficient Hoechst33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors[J]．Blood，2002，99(2)：507-512．.
13. Challen GA，Little MH．A side order of stem cells：the SP phenotype[J]．Stem Cells，2006，24(1)：3-12．.
14. Ahmed F，Arseni N，Glimm H，et al．Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors[J]．Stem Cells，2008，26(3)：810-818．.
15. Bhattacharya S，Das A，Mallya K，et al．Maintenance of retinal stem cells by Abcg2 is regulated by notch signaling[J]．J Cell Sci，2007，120(Pt 15)：2652-2662．.
16. Diestra JE，Scheffer GL，Catala I，et al．Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material[J]．J Pathol，2002， 198(2)：213-219．.
17. Chen Z，Liu F，Ren Q，et al．Suppression of ABCG2 inhibits cancer cell proliferation[J]．Int J Cancer，2010，126(4)：841851．.
18. Vlaming ML，Lagas JS，Schinkel AH．Physiological and pharmacological roles of ABCG2 (BCRP)：Recent findings in Abcg2 knockout mice[J]．Adv Drug Deliv Rev，2009，61(1)：14-25．.
19. Polgar O，Robey RW，Bates SE．ABCG2：structure，function and role in drug response[J]．Expert Opin Drug Metab Toxicol， 2008，4(1)：1-15．.
20. Rocchi E，Khodjakov A，Volk EL，et al．The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane[J]．Biochem Biophys Res Commun， 2000，271(1)：42-46．.
21. Zen Y，F(xiàn)ujii T，Yoshikawa S，et al．Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma[J]． Am J Pathol，2007，170(5)：1750-1762．.
  1. 1. Robey RW，Polgar O，Deeken J，et al．ABCG2：determining its relevance in clinical drug resistance[J]．Cancer Metastasis Rev， 2007，26(1)：39-57．.
  2. 2. Zhou S，Schuetz JD，Bunting KD，et al．The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype[J]．Nat Med，2001，7(9)：1028-1034．.
  3. 3. Ding XW，Wu JH，Jiang CP．ABCG2：a potential marker of stem cells and novel target in stem cell and cancer therapy[J]． Life Sci，2010，86(17-18)：631-637．.
  4. 4. Ross DD，Nakanishi T．Impact of breast cancer resistance protein on cancer treatment outcomes[J]．Methods Mol Biol，2010， 596：251-290．.
  5. 5. Dean M，F(xiàn)ojo T，Bates S．Tumour stem cells and drug resistance[J]．Nat Rev Cancer，2005，5(4)：275-284．.
  6. 6. 徐叔云，卞如濂，陳修．藥理實驗方法[ M]．第 2版．北京：人民衛(wèi)生出版社，1991：731．.
  7. 7. 劉寶瑞，王婷婷，錢曉萍．原發(fā)性肝癌分子靶向治療研究進(jìn)展[ J]．世界華人消化雜志，2009，17(10)：993-997．.
  8. 8. Li F，Tiede B，Massagué J，et al．Beyond tumorigenesis：cancer stem cells in metastasis[J]．Cell Res，2007，17(1)：3-14．.
  9. 9. Visvader JE，Lindeman GJ．Cancer stem cells in solid tumours： accumulating evidence and unresolved questions[J]．Nat Rev Cancer，2008，8(10)：755-768．.
  10. 10. Chiba T，Kita K，Zheng YW，et al．Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J]．Hepatology，2006，44(1)：240-251．.
  11. 11. Kim M，Turnquist H，Jackson J，et al．The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst33342 and is overexpressed in hematopoietic stem cells[J]．Clin Cancer Res，2002，8(1)：22-28．.
  12. 12. Scharenberg CW，Harkey MA,Torok-Storb B．The ABCG2 transporter is an efficient Hoechst33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors[J]．Blood，2002，99(2)：507-512．.
  13. 13. Challen GA，Little MH．A side order of stem cells：the SP phenotype[J]．Stem Cells，2006，24(1)：3-12．.
  14. 14. Ahmed F，Arseni N，Glimm H，et al．Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors[J]．Stem Cells，2008，26(3)：810-818．.
  15. 15. Bhattacharya S，Das A，Mallya K，et al．Maintenance of retinal stem cells by Abcg2 is regulated by notch signaling[J]．J Cell Sci，2007，120(Pt 15)：2652-2662．.
  16. 16. Diestra JE，Scheffer GL，Catala I，et al．Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material[J]．J Pathol，2002， 198(2)：213-219．.
  17. 17. Chen Z，Liu F，Ren Q，et al．Suppression of ABCG2 inhibits cancer cell proliferation[J]．Int J Cancer，2010，126(4)：841851．.
  18. 18. Vlaming ML，Lagas JS，Schinkel AH．Physiological and pharmacological roles of ABCG2 (BCRP)：Recent findings in Abcg2 knockout mice[J]．Adv Drug Deliv Rev，2009，61(1)：14-25．.
  19. 19. Polgar O，Robey RW，Bates SE．ABCG2：structure，function and role in drug response[J]．Expert Opin Drug Metab Toxicol， 2008，4(1)：1-15．.
  20. 20. Rocchi E，Khodjakov A，Volk EL，et al．The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane[J]．Biochem Biophys Res Commun， 2000，271(1)：42-46．.
  21. 21. Zen Y，F(xiàn)ujii T，Yoshikawa S，et al．Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma[J]． Am J Pathol，2007，170(5)：1750-1762．.