Abstract
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.
Highlights
Chemotherapy is the main means of cancer treatment, but it is impeded with the development of resistance to multiple chemotherapeutic drugs[1]
Though H460/MX20 cell xenograft had been used in some reports, most of these research was based on the hypothesis that H460/MX20 can maintain its resistance in vivo
Another study reported that human embryonic stem cells expressing ABC subfamily G member 2 (ABCG2) could tolerate the physical stress and UV irradiation much better than the ABCG2-negative cells[18]
Summary
Chemotherapy is the main means of cancer treatment, but it is impeded with the development of resistance to multiple chemotherapeutic drugs[1]. MDR is mainly due to the overexpression and regulation of the transmembrane ATP-binding cassette (ABC) transporters that function as active drug efflux pumps They pump anti-cancer agents from intracellular to extracellular space, causing resistance of tumor cells. Knockdown of ABCG2 by siRNA or inhibition of ABCG2 significantly restored the sensitivity of placental trophoblasts to apoptotic stress in response to cytokines[16] These studies strongly indicate that ABCG2 could play a key role in survival, which is much broader than its currently established role in drug efflux[19]. Establishing an ABCG2 overexpressing in vivo model would be effective and necessary for illustrating the mechanism of MDR, as well as giving support to further study the anti-apoptosis ability of specific cells. We established H460/ MX20 cell xenografts model in athymic nude mice and investigated the biological characteristics and the MDR phenotype of xenografts cells
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