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- Title
Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer.
- Authors
Jung, Minkyu; Park, Kyu Hyun; Kim, Hyun Myong; Kim, Tae Soo; Zhang, Xianglan; Park, Sun-Mi; Beom, Seung-Hoon; Kim, Hyo Song; Cheong, Jae-Ho; Chung, Hyun Cheol; Soong, John; Lin, Shu-chuan; Rha, Sun Young
- 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.
- Subjects
PROTEIN kinase CK2; PACLITAXEL; STOMACH cancer; CASEIN kinase; ANAPLASTIC thyroid cancer
- Publication
Gastric Cancer, 2019, Vol 22, Issue 6, p1153
- ISSN
1436-3291
- Publication type
Article
- DOI
10.1007/s10120-019-00971-7