Upregulation of integrin‑linked kinase enhances tumor progression in gemcitabine‑resistant pancreatic cancer

Pancreatic cancer (PaCa) tends to be resistant to chemotherapy and is associated with a very poor prognosis. It has been previously reported by the authors that integrin-linked kinase (ILK) is a prognostic factor in PaCa. ILK expression was examined in a newly established gemcitabine (Gem)-resistant (Gem-R) PaCa cell line and it was demonstrated that ILK expression was upregulated compared with that in Gem-sensitive (Gem-S) cells. In the present study, the effects of increased ILK expression in Gem-R PaCa cells were evaluated and it was examined whether compound 22 (Cpd22), an ILK inhibitor, exerted antitumor effects not only in Gem-S cells but also in Gem-R cells. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that ILK expression was higher in Gem-R PaCa cells than in Gem-S PaCa cells. Cpd22 inhibited the growth of PaCa cells in a concentration-dependent manner. Cpd22 also inhibited the growth of Gem-R PaCa cells. The invasive and angiogenic potential of Gem-R PaCa cells was enhanced compared with that in Gem-S cells; however, ILK small interfering RNA and Cpd22 treatment suppressed this enhancement of invasive potential compared with that in Gem-S cells. The addition of Cpd22 to Gem also improved the sensitivity of Gem-R cell lines to Gem. Furthermore, enhanced Akt signaling was associated with increased malignancy in Gem-R cell lines. In conclusion, ILK was upregulated with resistance and may be involved in tumor angiogenesis, invasive potential, and chemotherapy resistance, which were all suppressed by Cpd22 treatment. Thus, Cpd22 may be a novel therapeutic agent for the treatment of PaCa.

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