Chu M Y, Hagerty M G, Wiemann M C, Tibbetts L M, Sato S, Cummings F J, Bogaars H A, Leduc E H, Calabresi P
Cancer Res. 1985 Mar;45(3):1357-66.
Two human breast carcinoma cell lines, EP and MW, were established in culture from malignant pleural effusions. In addition to producing tumors in antithymocyte serum-immunosuppressed mice, both cell lines showed epithelial characteristics and anchorage-independent growth in soft agar. EP and MW differed in morphology (spindle-shaped versus round), chromosomal mode (hyperdiploid versus near triploid), estrogen receptor content (43.8 versus 5.1 fmol/mg protein), cloning efficiency (0.24 versus 15%), and activities (milliunits/10(6) cells) of creatine phosphokinase (25.7 versus 62.6) and lactate dehydrogenase (346.7 versus 778.5). Electron microscopy revealed that MW cells had more perinuclear filamentous material and more frequent intracytoplasmic vacuole formation than did EP cells. While having no effect on MW cells at the concentrations studied (10(-5) to 10(-11) M), beta-estradiol (10(-7) M) stimulated the growth of EP cells by 106% over the hormone-depleted control. In a variety of systems, EP was consistently the more drug sensitive of the two lines. In vitro, EP was significantly (p less than 0.001) more sensitive to methotrexate, vincristine, and 5-fluorouracil, respectively. In antithymocyte serum-mouse xenografts, EP displayed a greater response to three different dosages of a combination of cyclophosphamide, methotrexate, and 5-fluorouracil. One such dosage (cyclophosphamide, 32.0 mg/kg/day; methotrexate, 13.0 mg/kg/day; 5-fluorouracil, 190.0 mg/kg/day; for 1 day) reduced EP and MW tumor weights to 5.9 and 41% of controls, respectively. These results correlated well with the clinical responses.
从恶性胸腔积液中培养建立了两个人类乳腺癌细胞系,即EP和MW。这两个细胞系除了能在抗胸腺细胞血清免疫抑制的小鼠体内产生肿瘤外,还表现出上皮细胞特征以及在软琼脂中不依赖贴壁生长的特性。EP和MW在形态(纺锤形与圆形)、染色体模式(超二倍体与近三倍体)、雌激素受体含量(43.8与5.1 fmol/mg蛋白质)、克隆效率(0.24与15%)以及肌酸磷酸激酶(25.7与62.6)和乳酸脱氢酶(346.7与778.5)的活性(毫单位/10⁶个细胞)方面存在差异。电子显微镜显示,MW细胞比EP细胞有更多的核周丝状物质和更频繁的胞质内空泡形成。在所研究的浓度(10⁻⁵至10⁻¹¹ M)下,β-雌二醇(10⁻⁷ M)对MW细胞没有影响,但与激素缺乏的对照组相比,刺激EP细胞生长了106%。在各种系统中,EP始终是这两个细胞系中对药物更敏感的一个。在体外,EP对甲氨蝶呤、长春新碱和5-氟尿嘧啶分别显著(p<0.001)更敏感。在抗胸腺细胞血清-小鼠异种移植模型中,EP对三种不同剂量的环磷酰胺、甲氨蝶呤和5-氟尿嘧啶联合用药表现出更大的反应。其中一种剂量(环磷酰胺,32.0 mg/kg/天;甲氨蝶呤,13.0 mg/kg/天;5-氟尿嘧啶,190.0 mg/kg/天;用药1天)分别将EP和MW的肿瘤重量降低至对照组的5.9%和41%。这些结果与临床反应密切相关。