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Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer

Authors
 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 
Citation
 GASTRIC CANCER, Vol.22(6) : 1153-1163, 2019 
Journal Title
 GASTRIC CANCER 
ISSN
 1436-3291 
Issue Date
2019
Keywords
Casein kinase 2 ; Drug resistance ; Gastric cancer ; Paclitaxel
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.
Full Text
https://link.springer.com/article/10.1007%2Fs10120-019-00971-7
DOI
10.1007/s10120-019-00971-7
Appears in Collections:
7. Others (기타) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae Soo(김태수)
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Kyu Hyun(박규현)
Beom, Seung Hoon(범승훈) ORCID logo https://orcid.org/0000-0001-7036-3753
Zhang, Xiang Lan(장향란)
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173222
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