期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms22158041
关键词
low-molecular-weight fucoidan; colorectal cancer; HCT116 cell; Caco-2 cell; fluoropyrimidine-based chemotherapy; complementary therapy
资金
- Ministry of Science and Technology [MOST 109-2314-B-037-035, MOST 109-2314-B-037-040, MOST 109-2314-B-037-046-MY3]
- Ministry of Health and Welfare [MOHW107-TDU-B-212-123006, MOHW107-TDU-B-212-114026B, MOHW108-TDU-B-212-133006, MOHW109-TDU-B-212-134026, MOHW109-TDU-B-212-114006]
- health and welfare surcharge of on tobacco products
- Kaohsiung Medical University Hospital [KMUH109-9R32, KMUH109-9R33, KMUH109-9R34, KMUH109-9M30, KMUH109-9M31, KMUH109-9M32, KMUH109-9M33, KMUHS10903, KMUHSA10903, KMUH-DK(C)110010, KMUH-DK(B)110004-3]
- KMU Center for Cancer Research [KMU-TC109A04-1]
- KMU Center for Liquid Biopsy
- Cohort Research Center Grant [KMU-TC109B05]
- Kaohsiung Medical University
- Grant of Taiwan Precision Medicine Initiative, Academia Sinica, Taiwan, R.O.C.
In this study, low-molecular-weight fucoidan (LMWF) was found to enhance the anti-cancer effects of fluoropyrimidine-based chemotherapy through different mechanisms in colorectal cancer cells. LMWF enhanced cell viability suppression by inducing cell cycle arrest and late apoptosis in HCT116 cells, and by activating multiple signaling pathways in Caco-2 cells. Moreover, LMWF also inhibited tumor cell migration through specific signaling pathways in both cell types.
This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF--5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal-epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.
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