| Autor: |
Toyohiro Hirai, Young Hak Kim, Hironori Yoshida, Yuichi Sakamori, Takashi Nomizo, Yuto Yasuda, Hitomi Ajimizu, Tetsuya Oguri, Yasushi Yoshimura, Koh Furugaki, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1535-7163.c.6542827 |
| Popis: |
Alectinib is used as a first-line treatment for anaplastic lymphoma kinase (ALK)-rearranged non–small cell lung cancer (NSCLC). Whereas other ALK inhibitors have been reported to be involved in resistance to ATP-binding cassette (ABC) transporters, no data are available regarding the association between resistance to alectinib and ABC-transporters. To investigate whether ABC-transporters contribute to alectinib resistance, ABC-transporter expression in alectinib-resistant cell lines derived from a patient with ALK-rearranged NSCLC and from H2228 lung cancer cells was evaluated and compared with that in each parent cell type. ATP-binding cassette subfamily C member 11 (ABCC11) expression was significantly increased in alectinib-resistant cell lines compared with that in alectinib-sensitive lines. ABCC11 inhibition increased sensitivity to alectinib in vitro. ABCC11-overexpressing cells were established by transfection of an ABCC11 expression vector into H2228 cells, while control cells were established by transfecting H2228 cells with an empty vector. ABCC11-overexpressing cells exhibited decreased sensitivity to alectinib compared with that of control cells in vitro. Moreover, the tumor growth rate following alectinib treatment was higher in ABCC11-overexpressing cells than that in control cells in vivo. In addition, the intracellular alectinib concentration following exposure to 100 nmol/L alectinib was significantly lower in the ABCC11-overexpressing cell line compared with that in control cells. This is the first preclinical evidence showing that ABCC11 expression may be involved in acquired resistance to alectinib. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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