Wang Fang, Liang Yong-Ju, Wu Xing-Ping, Su Xiao-Dong, Fu Li-Wu
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.
Chin J Cancer. 2012 Mar;31(3):150-8. doi: 10.5732/cjc.011.10310. Epub 2012 Feb 24.
S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.
S1-M1-80细胞源自人结肠癌S1细胞,是通过米托蒽醌筛选出的过表达ABCG2的细胞,广泛用于多药耐药(MDR)的体外研究。在本研究中,建立了S1-M1-80细胞异种移植模型,以研究MDR表型和细胞生物学特性在体内是否得以维持。我们的结果表明,S1-M1-80细胞的增殖、细胞周期和ABCG2表达水平与从S1-M1-80细胞异种移植瘤中分离出的细胞(命名为xS1-M1-80细胞)相似。一致地,xS1-M1-80细胞对米托蒽醌和拓扑替康等ABCG2底物表现出高水平耐药,但对非ABCG2底物顺铂仍敏感。此外,特异性ABCG2抑制剂Ko143可有效使xS1-M1-80细胞对米托蒽醌和拓扑替康敏感。这些结果表明,裸鼠体内的S1-M1-80细胞异种移植瘤在9周时保留了其原始细胞学特征。因此,该模型可作为进一步研究ABCG2介导的MDR的良好系统。