Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer

Minkyu Jung, Kyu Hyun Park, Hyun Myong Kim, Tae Soo Kim, Xianglan Zhang, Sun Mi Park, Seung Hoon Beom, Hyo Song Kim, Jae Ho Cheong, Hyun Cheol Chung, John Soong, Shu chuan Lin, Sun Young Rha

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2 Citations (Scopus)

Abstract

Purpose: Casein kinase (CK) 2 activation has been implicated in the proliferation of various tumor types and resistance to chemotherapy. We investigated the mechanistic basis for the association between CK2 activation and paclitaxel resistance in a gastric cancer (GC). Experimental design: CK2 expression was evaluated in 59 advanced GC patients treated with paclitaxel as the second-line therapy. The efficacy of a CK2 inhibitor, CX-4945, and paclitaxel was evaluated in GC cell lines and a xenograft model. Results: Patients with high CK2 expression (29/59, 39%) showed lower disease control rates (47.7% vs. 72.3%, p = 0.017) and shorter progression-free survival (2.8 vs. 4.8 months, p = 0.009) than patients with low CK2 expression. CK2 protein expression was associated with sensitivity to paclitaxel in 49 GC cell lines. Combination therapy with CX-4945 and paclitaxel exerted synergistic antiproliferative effects and inhibited the downregulation of phosphatidylinositol 3-kinase/AKT signaling in SNU-1 cells. In the SNU-1 xenograft model, the combination treatment was significantly superior to either single agent, suppressing tumor growth without notable toxicities. Conclusions: These results demonstrated that CK2 activation was related to paclitaxel resistance and that CX-4945 in combination with paclitaxel could be used as a potential treatment for paclitaxel resistance in GC.

Original languageEnglish
Pages (from-to)1153-1163
Number of pages11
JournalGastric Cancer
Volume22
Issue number6
DOIs
Publication statusPublished - 2019 Nov 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology
  • Cancer Research

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    Jung, M., Park, K. H., Kim, H. M., Kim, T. S., Zhang, X., Park, S. M., Beom, S. H., Kim, H. S., Cheong, J. H., Chung, H. C., Soong, J., Lin, S. C., & Rha, S. Y. (2019). Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer. Gastric Cancer, 22(6), 1153-1163. https://doi.org/10.1007/s10120-019-00971-7