Open Access

Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines

  • Authors:
    • Baojun Ren
    • Yan Geng
    • Shuxiang Chen
    • Zhuowei Gao
    • Kehong Zheng
    • Yong Yang
    • Qimei Luo
    • Jing Feng
    • Zhentao Luo
    • Yongle Ju
    • Zonghai Huang
  • View Affiliations

  • Published online on: April 11, 2023     https://doi.org/10.3892/etm.2023.11942
  • Article Number: 243
  • Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to examine the effects of alisertib (ALS) on RAS signaling pathways against a panel of colorectal cancer (CRC) cell lines and engineered Flp‑In stable cell lines expressing different Kirsten rat sarcoma virus (KRAS) mutants. The viability of Caco‑2KRAS wild‑type, Colo‑678KRAS G12D, SK‑CO‑1KRAS G12V, HCT116KRAS G13D, CCCL‑18KRAS A146T and HT29BRAF V600E cells was examined by Cell Titer‑Glo assay, and that of stable cell lines was monitored by IncuCyte. The expression levels of phosphorylated (p‑)Akt and p‑Erk as RAS signal outputs were measured by western blotting. The results suggested that ALS exhibited different inhibitory effects on cell viability and different regulatory effects on guanosine triphosphate (GTP)‑bound RAS in CRC cell lines. ALS also exhibited various regulatory effects on the PI3K/Akt and mitogen‑activated protein kinase (MAPK) pathways, the two dominant RAS signaling pathways, and induced apoptosis and autophagy in a RAS allele‑specific manner. Combined treatment with ALS and selumetinib enhanced the regulatory effects of ALS on apoptosis and autophagy in CRC cell lines in a RAS allele‑specific manner. Notably, combined treatment exhibited a synergistic inhibitory effect on cell proliferation in Flp‑In stable cell lines. The results of the present study suggested that ALS differentially regulates RAS signaling pathways. The combined approach of ALS and a MEK inhibitor may represent a new therapeutic strategy for precision therapy for CRC in a KRAS allele‑specific manner; however, this effect requires further study in vivo.
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June-2023
Volume 25 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Ren B, Geng Y, Chen S, Gao Z, Zheng K, Yang Y, Luo Q, Feng J, Luo Z, Ju Y, Ju Y, et al: Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines. Exp Ther Med 25: 243, 2023
APA
Ren, B., Geng, Y., Chen, S., Gao, Z., Zheng, K., Yang, Y. ... Huang, Z. (2023). Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines. Experimental and Therapeutic Medicine, 25, 243. https://doi.org/10.3892/etm.2023.11942
MLA
Ren, B., Geng, Y., Chen, S., Gao, Z., Zheng, K., Yang, Y., Luo, Q., Feng, J., Luo, Z., Ju, Y., Huang, Z."Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines". Experimental and Therapeutic Medicine 25.6 (2023): 243.
Chicago
Ren, B., Geng, Y., Chen, S., Gao, Z., Zheng, K., Yang, Y., Luo, Q., Feng, J., Luo, Z., Ju, Y., Huang, Z."Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines". Experimental and Therapeutic Medicine 25, no. 6 (2023): 243. https://doi.org/10.3892/etm.2023.11942