• 中國(guó)醫(yī)學(xué)科學(xué)院中國(guó)協(xié)和醫(yī)科大學(xué)北京協(xié)和醫(yī)院基本外科（北京100730）;

【摘要】目的建立人胰腺癌阿霉素(ADM)耐藥細(xì)胞株SW1990/ADM，探討其耐藥機(jī)理。
方法采用ADM體外濃度梯度倍增法誘導(dǎo)培養(yǎng)人胰腺癌細(xì)胞株SW1990 10個(gè)月，獲得耐藥細(xì)胞株SW1990/ADM，脫藥培養(yǎng)2 個(gè)月后檢測(cè)其生物學(xué)性狀、藥物敏感性及多藥耐藥基因mdr1的功能及表達(dá)情況。
結(jié)果與親本細(xì)胞株SW1990相比，SW1990/ADM在形態(tài)學(xué)上發(fā)生了一系列變化； 對(duì)包括ADM在內(nèi)的多種化療藥物均表現(xiàn)出一定的耐藥性，其對(duì)ADM、絲裂霉素、氟尿嘧啶和健擇的耐藥指數(shù)分別達(dá)到49.60、 7.25、 3.80和 1.25； 其mdr1 mRNA的表達(dá)亦明顯高于親本細(xì)胞株SW1990(P＜0.01）。
結(jié)論體外濃度梯度倍增法可建立穩(wěn)定傳代的人胰腺癌耐藥細(xì)胞株SW1990/ADM。其耐藥性與mdr1的表達(dá)呈正相關(guān)。

引用本文： 張立陽(yáng),趙玉沛,吳元德,廖泉,郭俊超,劉子文,張?zhí)? 胰腺癌阿霉素耐藥細(xì)胞株SW1990/ADM的建立及其耐藥機(jī)理研究. 中國(guó)普外基礎(chǔ)與臨床雜志, 2005, 12(1): 46-50. doi: 復(fù)制

1. Fillpits M, Suchomel RW, Dekan G, et al. Expression of the multidrug resistanceassociated protein (MRP) gene in colorectal carcinomas [Ｊ]. Br J Cancer, 1997; 75(2)∶208.
2. 張立陽(yáng),趙玉沛,廖泉,等. MDR1在胰腺癌細(xì)胞株中的表達(dá)及其意義 [Ｊ]. 中華實(shí)驗(yàn)外科雜志， 2003； 20（5）∶475.
3. Jokoby WB. Methods in enzymology [M]. New York: Acad Press,1979∶150.
4. Hansen MB, Nielsen SE, Berg K. Reexamination and further development of a precise and rapid dye method for measuring cell growth/cell kill [Ｊ]. J Immunol Methods, 1989; 119(2)∶203.
5. Biedler JL, Riehm H. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: crossresistance, radioautographic, and cytogenetic studies [Ｊ]. Cancer Res, 1970; 30(4)∶1174.
6. Suwa H, Ohshio G, Arao S, et al. Immunohistochemical localization of Pglycoprotein and expression of the multidrug resistance1 gene in human pancreatic cancer: relevance to indicator of better prognosis [Ｊ]. Jpn J Cancer Res, 1996; 87(6)∶641.
7. 易善紅,楊唐俊, 何斌,等. 體內(nèi)基因轉(zhuǎn)移建立多藥耐藥性人膀胱癌裸鼠荷瘤模型 [Ｊ]. 中華泌尿外科雜志, 2000; 21(9)∶547.
8. Yu DS, Chang SY, Ma CP. Characterization and modulation of transitional cell carcinoma cell lines with acquired multidrug resistance [Ｊ]. Br J Urol, 1998; 81(2)∶234.
9. 梁正東，卞度宏. 卵巢癌細(xì)胞對(duì)順鉑耐藥及其逆轉(zhuǎn)的實(shí)驗(yàn)研究 [Ｊ]. 中華婦產(chǎn)科雜志，1996； 31(2)∶75.
10. Moran E, Cleary I, Larkin AM, et al. Coexpression of MDRassociated markers, including P170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42 [Ｊ]. Eur J Cancer, 1997; 33(4)∶652.
11. UchiyamaKokubu N, Watanabe T. Establishment and characterization of adriamycinresistant human colorectal adenocarcinoma HCT15 cell lines with multidrug resistance [Ｊ]. Anticancer Drugs, 2001; 12(9)∶769.
  1. 1. Fillpits M, Suchomel RW, Dekan G, et al. Expression of the multidrug resistanceassociated protein (MRP) gene in colorectal carcinomas [Ｊ]. Br J Cancer, 1997; 75(2)∶208.
  2. 2. 張立陽(yáng),趙玉沛,廖泉,等. MDR1在胰腺癌細(xì)胞株中的表達(dá)及其意義 [Ｊ]. 中華實(shí)驗(yàn)外科雜志， 2003； 20（5）∶475.
  3. 3. Jokoby WB. Methods in enzymology [M]. New York: Acad Press,1979∶150.
  4. 4. Hansen MB, Nielsen SE, Berg K. Reexamination and further development of a precise and rapid dye method for measuring cell growth/cell kill [Ｊ]. J Immunol Methods, 1989; 119(2)∶203.
  5. 5. Biedler JL, Riehm H. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: crossresistance, radioautographic, and cytogenetic studies [Ｊ]. Cancer Res, 1970; 30(4)∶1174.
  6. 6. Suwa H, Ohshio G, Arao S, et al. Immunohistochemical localization of Pglycoprotein and expression of the multidrug resistance1 gene in human pancreatic cancer: relevance to indicator of better prognosis [Ｊ]. Jpn J Cancer Res, 1996; 87(6)∶641.
  7. 7. 易善紅,楊唐俊, 何斌,等. 體內(nèi)基因轉(zhuǎn)移建立多藥耐藥性人膀胱癌裸鼠荷瘤模型 [Ｊ]. 中華泌尿外科雜志, 2000; 21(9)∶547.
  8. 8. Yu DS, Chang SY, Ma CP. Characterization and modulation of transitional cell carcinoma cell lines with acquired multidrug resistance [Ｊ]. Br J Urol, 1998; 81(2)∶234.
  9. 9. 梁正東，卞度宏. 卵巢癌細(xì)胞對(duì)順鉑耐藥及其逆轉(zhuǎn)的實(shí)驗(yàn)研究 [Ｊ]. 中華婦產(chǎn)科雜志，1996； 31(2)∶75.
  10. 10. Moran E, Cleary I, Larkin AM, et al. Coexpression of MDRassociated markers, including P170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42 [Ｊ]. Eur J Cancer, 1997; 33(4)∶652.
  11. 11. UchiyamaKokubu N, Watanabe T. Establishment and characterization of adriamycinresistant human colorectal adenocarcinoma HCT15 cell lines with multidrug resistance [Ｊ]. Anticancer Drugs, 2001; 12(9)∶769.