Open Access

Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2‑STAT1‑Mcl‑1 axis

  • Authors:
    • Xia Li
    • Zhe Wang
    • Shengjie Zhang
    • Qinghua Yao
    • Wei Chen
    • Feiyan Liu
  • View Affiliations

  • Published online on: March 4, 2021     https://doi.org/10.3892/ol.2021.12613
  • Article Number: 352
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Under pathological conditions, the Janus kinase (JAK)/STAT signaling pathway can regulate the proliferation, differentiation and migration of tumor cells, including colorectal cancer (CRC). CRC is the third major types of cancer among males and the second among females worldwide. In China, CRC is the fifth common cancer among both males and females. Western blotting, flow cytometry, RNA interference, immunoprecipitation, xenografts models, and immunohistochemical staining were carried out to evaluate the possible mechanisms of acton of ruxolitinib. The present data suggested that ruxolitinib can suppress CRC cell proliferation by inducing apoptosis. Firstly, JAK1/2‑STAT1 was identified as the target of ruxolitinib. Then, ruxolitinib downregulated myeloid cell leukemia‑1 (Mcl‑1) mRNA level and decreased its protein level, which enabled Bak to trigger CRC apoptosis. Furthermore, ruxolitinib exerted potent activity against CRC xenograft growth in vivo. High expression of phosphorylated STAT1 (S727) was also confirmed in 44 pairs of human colon carcinoma and adjacent normal tissues. Taken together, the results showed that ruxolitinib decreased JAK1/2‑STAT1‑Mcl‑1 protein level and effectively suppressed CRC cell proliferation in vitro and in vivo. Therefore, ruxolitinib could be a promising anticancer agent for CRC treatment.
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May-2021
Volume 21 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Li X, Wang Z, Zhang S, Yao Q, Chen W and Liu F: Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2‑STAT1‑Mcl‑1 axis. Oncol Lett 21: 352, 2021
APA
Li, X., Wang, Z., Zhang, S., Yao, Q., Chen, W., & Liu, F. (2021). Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2‑STAT1‑Mcl‑1 axis. Oncology Letters, 21, 352. https://doi.org/10.3892/ol.2021.12613
MLA
Li, X., Wang, Z., Zhang, S., Yao, Q., Chen, W., Liu, F."Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2‑STAT1‑Mcl‑1 axis". Oncology Letters 21.5 (2021): 352.
Chicago
Li, X., Wang, Z., Zhang, S., Yao, Q., Chen, W., Liu, F."Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2‑STAT1‑Mcl‑1 axis". Oncology Letters 21, no. 5 (2021): 352. https://doi.org/10.3892/ol.2021.12613