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BMC Res Notes. 2019 Mar 11;12(1):125. doi: 10.1186/s13104-019-4163-x.

INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification.

Author information

1
Hallym Translational Research Institute, Hallym University Sacred Heart Hospital, Anyang, 14066, Republic of Korea.
2
Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14086, Republic of Korea.
3
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, 689-798, Republic of Korea.
4
Korea Basic Research Institute Seoul Center, Seoul, 02855, Republic of Korea.
5
Department of Bio-medical Gerontology, Ilsong Institute of Life Sciences, Hallym University, Anyang, Gyeonggi-do, 14066, Republic of Korea.
6
Hallym Translational Research Institute, Hallym University Sacred Heart Hospital, Anyang, 14066, Republic of Korea. fhdzang@hallym.or.kr.
7
Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14086, Republic of Korea. fhdzang@hallym.or.kr.

Abstract

OBJECTIVE:

Gastric cancer is more open related to genetic predisposition. In our RNA sequencing study on gastric cancer patients, Runt-related transcription factor-3 (RUNX3) expression was significantly down-regulated in gastric cancer. We showed that decreased levels of RUNX3 are significantly associated with c-MET (r = - 0.4216, P = 0.0130). In addition, c-MET expression is a candidate for targeted therapy in gastric cancer. Therefore, in the present study, the anti-cancer effects of the c-MET inhibitor on gastric cancer cells from positive or negative for c-MET amplification were evaluated.

RESULTS:

INC280 treatment inhibits growth of a c-MET-amplified MKN45 (RUNX3-positive) and SNU620 (RUNX3-negative) diffuse type cells. Then, INC280 showed the highest inhibition and apoptotic rates with the lowest IC50s in MKN45 cells but not in c-MET-reduced MKN28 (intestinal type) cells. We also showed that INC280 inhibits the WNT signaling pathway and SNAIL expression in MKN45 cells. The data indicate that INC280 could be used as therapeutic agents for the prevention or treatment of diffuse gastric cancer positive for c-MET amplification.

KEYWORDS:

Diffuse type; Gastric cancer; INC280; RUNX3; c-MET

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