Experimental Animal Center, Sun Yat-sen University, Guangzhou, 510080, China.
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
Sci Rep. 2017 Jan 6;7:40064. doi: 10.1038/srep40064.
H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone's induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro. Importantly, xH460/MX20 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan as H460/MX20 cells did. Furthermore, lapatinib, the inhibitor of ABCG2, potently reversed mitoxantrone- and topotecan-resistance of xH460/MX20 cells. Taken together, these results suggest that H460/MX20 cell xenografts in athymic nude mice still retain their original cytological characteristics and MDR phenotype. Thus, the H460/MX20 cell xenografts model could serve as a sound model in vivo for study on reversal MDR.
H460/MX20 细胞株来源于人肺大细胞癌 H460 细胞系,经米托蒽醌诱导后转化为 ABCG2 过表达细胞,广泛应用于体外多药耐药(MDR)的研究。为了建立和传播 H460/MX20 细胞异种移植模型,我们研究了体内模型中细胞生物学特性和 MDR 表型是否得到维持。我们的结果表明,从 H460/MX20 细胞异种移植中分离的 xH460/MX20 细胞的细胞增殖、细胞周期和 ABCG2 表达水平与体外的 H460/MX20 细胞相似。重要的是,xH460/MX20 细胞对 ABCG2 底物(如米托蒽醌和拓扑替康)的耐药性与 H460/MX20 细胞相当。此外,ABCG2 抑制剂拉帕替尼可有效逆转 xH460/MX20 细胞对米托蒽醌和拓扑替康的耐药性。综上所述,这些结果表明,裸鼠皮下 H460/MX20 细胞异种移植仍保留其原始细胞学特征和 MDR 表型。因此,H460/MX20 细胞异种移植模型可作为体内研究逆转 MDR 的良好模型。