RT Journal Article
SR Electronic
T1 CJ14939, a Novel JAK Inhibitor, Increases Oxaliplatin-induced Cell Death Through JAK/STAT Pathway in Colorectal Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1813
OP 1819
DO 10.21873/anticanres.15657
VO 42
IS 4
A1 HONG, JUN KI
A1 KIM, DO YEON
A1 SHIN, JAE-SIK
A1 RYU, YEA SEONG
A1 MOON, JAI-HEE
A1 KOH, DONG-IN
A1 LEE, SEUL
A1 LEE, JINWOO
A1 LEE, WON JUN
A1 LEE, EUN YOUNG
A1 JUNG, SOO-A
A1 KIM, SEUNG CHAN
A1 YU, HA NA
A1 KIM, MI JIN
A1 HONG, SEUNG-WOO
A1 PARK, SANG SOO
A1 JUNG, JOONYEE
A1 KIM, SEUNG MI
A1 KIM, EUN HO
A1 JEONG, HONG-RAE
A1 GONG, JI HEE
A1 KIM, JIEUN
A1 KIM, TAE WON
A1 JIN, DONG-HOON
YR 2022
UL http://ar.iiarjournals.org/content/42/4/1813.abstract
AB Background/Aim: Colorectal cancer is reported to have the highest mortality rate among human malignancies. Although many research results for the treatment of colorectal cancer have been reported, there is no suitable treatment when resistance has developed. Therefore, it is necessary to develop new therapeutic agents. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling plays an essential role in cell differentiation, proliferation, and survival. Abnormal activation of the JAK/STAT signaling pathway, by gene mutation or amplification, may induce cancer development, and sustained JAK/STAT activation is involved in chemoresistance. While many therapeutic agents have been developed to treat colon cancer, there remains no drug to overcome resistance to chemotherapies. The purpose of this study was to determine the potential of CJ14939 as a novel JAK inhibitor for the treatment of colorectal cancer. Materials and Methods: In this study, cell culture, cell death assay, 3- (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, colony formation assay, immunoblot analysis and tumor xenograft were applied. Results: CJ14939 induced cell death, and inhibited phosphorylation of JAK1 and STAT3 in colorectal cancer cells. Furthermore, CJ14939 also promoted oxaliplatin-induced cell death, up-regulated expression of cleaved caspase-3, and down-regulated expression of phospho-JAK1 and phospho-STAT3. In vivo, co-treatment with CJ14939 and oxaliplatin notably reduced tumor growth when compared with CJ14939 or oxaliplatin treatment alone. Conclusion: This study identifies the important potential of CJ14939 in colorectal cancer treatment and suggests that combining CJ14939 with oxaliplatin might be a novel therapeutic strategy for patients with colorectal cancer.