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Biosci Rep. 2019 Mar 6;39(3). pii: BSR20181786. doi: 10.1042/BSR20181786. Print 2019 Mar 29.

KRAS-mutant colon cancer cells respond to combined treatment of ABT263 and axitinib.

Author information

1
Department of Laboratory Medicine Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, JS, People's Republic of China.
2
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China.
3
Department of Laboratory Medicine Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, JS, People's Republic of China xudong_wang11@163.com.
4
Clinical Tissue Bank, Department of Pathology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, JS, People's Republic of China.

Abstract

Significant challenges to develop selective and effective pharmacological inhibitors for important oncoproteins like RAS continue impeding the success to treat cancers driven by such mutations. In the present study, the ABT263 and axitinib combination imposed synergistic effects on RAS-mutant colon cancer cells. The combination inhibited in vitro and in vivo growth of the cancer cells by enhancing apoptosis. Furthermore, AKT and Wnt/β-catenin signaling pathways were slightly down-regulated by the combination in KRAS-mutant colon cancer cells. The current results indicate that oncogene addiction can be targeted for therapy in colon cancer cells harboring the RAS-mutant. Therefore, targeting oncogene addiction can be a viable strategy for treating refractory cancers driven by important oncogenes, such as KRAS, which are otherwise difficult to be targeted by small molecules.

KEYWORDS:

ABT263; KRAS-mutant colon cancer; axitinib; combination index; combination treatment; synergy

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