TY - JOUR AB - The present study aimed to investigate whether the Janus‑activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a critical mechanism underlying the cancer‑associated fibroblast (CAF)‑induced chemoresistance of gastric cancer (GC). In addition, the present study tried to suggest a natural product to compromise the effects of CAF on the chemoresistance of GC. The results of cell proliferation assay revealed that the conditioned medium (CM) collected from CAFs further increased resistance to 5‑fluorouracil (5‑FU) in GC cell lines. Secretome analysis revealed that the levels of several secreted proteins, including C‑C motif chemokine ligand 2, C‑X‑C motif chemokine ligand 1, interleukin (IL)‑6 and IL‑8, were increased in the CM from CAFs co‑cultured with cancer cells compared to CM from cancer cells. Western blot analysis revealed that CAFs activated the JAK/STAT3 signaling pathway in cancer cells. The experimental models revealed that curcumin abrogated the CAF‑mediated activation of the JAK/STAT3 signaling pathway in GC cells. In vivo data revealed the synergistic effects of curcumin with 5‑FU treatment in xenograft GC tumors. These data strongly suggest that the suppression of the JAK/STAT3 signaling pathway counteracts the CAF‑induced chemoresistance of GC cells. It is suggested that curcumin may be a suitable natural product which may be used to overcome chemoresistance by inhibiting the CAF‑induced activation of the JAK/STAT3 signaling pathway in GC. AD - Department of Surgery, Ajou University School of Medicine, Suwon, Gyeonggi‑do 16499, Republic of Korea Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 16591, Republic of Korea Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Gyeonggi‑do 16499, Republic of Korea AU - Ham,In-Hye AU - Wang,Lei AU - Lee,Dagyeong AU - Woo,Jongsu AU - Kim,Tae,Hoon AU - Jeong,Hye,Young AU - Oh,Hye,Jeong AU - Choi,Kyeong,Sook AU - Kim,Tae-Min AU - Hur,Hoon DA - 2022/07/01 DO - 10.3892/ijo.2022.5375 IS - 1 JO - Int J Oncol KW - gastric cancer cancer‑associated fibroblast curcumin chemoresistance tumor microenvironment PY - 2022 SN - 1019-6439 1791-2423 SP - 85 ST - Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway T2 - International Journal of Oncology TI - Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway UR - https://doi.org/10.3892/ijo.2022.5375 VL - 61 ER -