OncoTargets and Therapy 2015-01-01

Role of integrin-linked kinase in drug resistance of lung cancer.

Zhiyang Jia

文献索引：Onco. Targets Ther. 8 , 1561-5, (2015)

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摘要

The objective of the present investigation was to investigate the role of integrin-linked kinase (ILK) in the gemcitabine-resistant lung cancer cell line A549 and explore the underlying mechanism.Gemcitabine-resistant A549 (A549/GemR) cell line was established by pulse-exposed to moderate concentration of gemcitabine (Gem), and the drug resistant index was measured by MTT assay. Expression of ILK in A549/GemR cell line was detected by Western blot and real-time PCR. An ILK gene-silencing cell line was constructed using lentivirus-coated ILK shRNA. MTT assay was used to detect the drug sensitivity of the A549/GemR cell line to Gem after the ILK gene silencing. Western blot was used to measure the expression of E-cadherin, fibronectin, and MRP1 (multidrug resistance-associated protein 1) after silencing the ILK gene.The drug resistance index of A549/GemR was 13.5, and the messenger RNA and protein level of ILK was increased in A549/GemR. IC50 (half maximal inhibitory concentration) decreased from 14.69 to 4.13 mg/L when ILK was knocked down in A549/GemR. The expression of fibronectin and MRP1 was upregulated and E-cadherin expression was downregulated in A549/GemR, and these changes were reversed after ILK was knocked down.ILK was involved in drug resistance to Gem in lung cancer, and this function may be mediated by epithelial-mesenchymal transition and the MRP1 pathway.