{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:36:18Z","timestamp":1760060178025,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2018R1D1A1B07050210","K2407141","K2507511"],"award-info":[{"award-number":["2018R1D1A1B07050210","K2407141","K2507511"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Research-Driven Hospital","award":["2018R1D1A1B07050210","K2407141","K2507511"],"award-info":[{"award-number":["2018R1D1A1B07050210","K2407141","K2507511"]}]},{"DOI":"10.13039\/100016989","name":"Korea University Medicine","doi-asserted-by":"publisher","award":["2018R1D1A1B07050210","K2407141","K2507511"],"award-info":[{"award-number":["2018R1D1A1B07050210","K2407141","K2507511"]}],"id":[{"id":"10.13039\/100016989","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea University Guro Hospital","award":["2018R1D1A1B07050210","K2407141","K2507511"],"award-info":[{"award-number":["2018R1D1A1B07050210","K2407141","K2507511"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Colorectal cancer (CRC) remains a significant global health concern, with limited treatment options for metastatic stage 4 CRC. Fibroblast Growth Factor Receptor (FGFR) is a promising therapeutic target in CRC, while cannabidiol (CBD) has shown potential for inducing cell death and overcoming drug resistance. This study evaluates the efficacy of FGFR inhibitors and explores the synergistic effects of combining FGFR inhibitors with CBD in inducing apoptosis in CRC cells. Methods: Cannabidiol and FGFR inhibitors were applied, and protein expression was analyzed via Western blot. Cell viability was assessed using the WST-1 assay, while apoptosis was measured through flow cytometry using Annexin V-FITC\/PI staining. CHOP-specific siRNA transfection was performed to study gene silencing effects, followed by RNA sequencing for differential expression and pathway analysis. Statistical significance was determined using ANOVA and t-tests, with p &lt; 0.05. Results: FGFR expression patterns were confirmed in various cancer cell lines, with NCI-H716 showing high FGFR2 expression. Treatment with CBD (4 \u00b5M) and AZD4547 (10 nM) resulted in significant cell death, especially when used in combination, indicating the effectiveness of this combined therapy. Increased apoptosis in NCI-H716 cells was confirmed with the combined treatment. RNA sequencing and heatmap analysis suggested that ER stress might be related to the observed synergistic effect. The role of ER stress in the combination-induced apoptosis of NCI-H716 cells was further validated. Conclusions: The combination of FGFR inhibitors and cannabidiol exhibited a synergistic effect in inducing cell death in colorectal cancer cells, likely through the ER stress pathway. This study supports the potential of combined FGFR inhibitor and CBD therapy as a promising strategy for enhancing anticancer effects in CRC.<\/jats:p>","DOI":"10.3390\/nu17162609","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T07:53:44Z","timestamp":1754985224000},"page":"2609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Anticancer Effects of Fibroblast Growth Factor Receptor Inhibitor and Cannabidiol in Colorectal Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7174-1218","authenticated-orcid":false,"given":"Yeonuk","family":"Ju","sequence":"first","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3793-7847","authenticated-orcid":false,"given":"Bu Gyeom","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Convergence New Drug Development, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong-An","family":"Gim","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Soonchunhyang University, Seoul 31538, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Woo","family":"Bong","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin Ock","family":"Cheong","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Cheul","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-8831","authenticated-orcid":false,"given":"Sang Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Wook","family":"Min","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5286-8042","authenticated-orcid":false,"given":"Sun Il","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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