Combined treatment of ABT199 and irinotecan suppresses KRAS-mutant lung cancer cells

  • Gene. 2019 Mar 10;688:1-6. doi: 10.1016/j.gene.2018.11.018.
Yinhai Xu  1 ,  Shuai Zong  1 ,  Xin Gao  2 ,  Haoliang Zhang  1 ,  Bin Wang  1 ,  Pengpeng Li  1 ,  Tielong Liu  2 ,  Shibao Li  3
Affiliations
  • 1. Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
  • 2. Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
  • 3. Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; Medical Technology Institute of Xuzhou Medical University, Xuzhou 221004, China. Electronic address: [email protected].
PMID: 30415007 DOI: 10.1016/j.gene.2018.11.018
Abstract

Lung Cancer has become the most prevalent neoplasm throughout the world with 1,2 million deaths per year. Molecular genetic analyses have suggested that KRAS mutation is much more frequency in NSCLC. Significant challenges are to develop selective pharmacological inhibitors for Ras mutation to treat cancers driven. In our study, we used the combinatorial strategy to target oncogene addiction for RAS-mutant cells and the data showed that ABT199 and irinotecan leads to RAS-mutant lung Cancer cell growth inhibition and enhanced Apoptosis in vitro and in vivo. Furthermore, PI3K/Akt signaling was down-regulated by the combination in KRAS-mutant lung Cancer cells. Importantly, the effects of ABT199 and irinotecan combination are synergistic on the RAS-mutant lung Cancer cells. Therefore, the combination suggests a strong synergy in vivo and a potential avenue for therapeutic treatment of KRAS-mutant cancers which are otherwise difficult targeted by small molecules.

Keywords
ABT199; Irinotecan; KRAS-mutant; PI3K/AKT signaling.
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