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CJ14939, a Novel JAK Inhibitor, Increases Oxaliplatin-induced Cell Death Through JAK/STAT Pathway in Colorectal

Jun Ki Hong1,2, DO Yeon Kim1,2, Jae-Sik Shin1

  • 1Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.

Anticancer Research
|March 29, 2022
PubMed
Abstract

Insights

CJ14939, a novel Janus kinase (JAK) inhibitor, effectively reduces colorectal cancer cell viability and enhances chemotherapy response. Combining CJ14939 with oxaliplatin shows significant potential for treating chemoresistant colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Colorectal cancer (CRC) has a high mortality rate, with limited treatment options for chemoresistant cases.
  • The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial in cell regulation and implicated in CRC development and chemoresistance.
  • Existing CRC therapies lack efficacy against drug-resistant tumors, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate CJ14939, a novel JAK inhibitor, as a potential therapeutic agent for colorectal cancer.
  • To investigate the efficacy of CJ14939 in overcoming chemoresistance in colorectal cancer models.
  • To explore the combination therapy of CJ14939 with oxaliplatin for enhanced colorectal cancer treatment.

Main Methods:

  • Cell viability and death assays were performed on colorectal cancer cell lines.
  • In vitro assays included MTT, colony formation, and immunoblotting to assess JAK/STAT pathway inhibition.
  • In vivo efficacy was evaluated using colorectal cancer tumor xenograft models in combination with oxaliplatin.

Main Results:

  • CJ14939 demonstrated potent inhibition of JAK1 and STAT3 phosphorylation in colorectal cancer cells, leading to cell death.
  • CJ14939 enhanced oxaliplatin-induced cytotoxicity by upregulating cleaved caspase-3 and downregulating phospho-JAK1/STAT3.
  • Combined treatment with CJ14939 and oxaliplatin significantly suppressed tumor growth in vivo compared to monotherapy.

Conclusions:

  • CJ14939 exhibits significant potential as a novel therapeutic agent for colorectal cancer.
  • Combination therapy with CJ14939 and oxaliplatin represents a promising strategy for overcoming chemoresistance in colorectal cancer.
  • Targeting the JAK/STAT pathway with CJ14939 offers a new avenue for colorectal cancer treatment.
Keywords:
CJ14939JAK inhibitorJAK/STATcolorectal canceroxaliplatin

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