title: An apple oligogalactan enhances the growth inhibitory effect of 5-fluorouracil on colorectal cancer.
abstract: Treatment of colorectal cancer (CRC) remains a clinical challenge, since current therapies are associated with obvious side effects and high expenses. These limitations highlight an urgent need for developing novel and safe treatment strategies. It is suggested that combinatorial strategies could be more effective and much safer than monotherapy in cancer treatment. In our previous study, an apple oligogalactan (AOG) has been found to show beneficial effect on treating CRC. This study tried to investigate whether AOG could enhance the growth inhibitory effect of 5-FU in human CRC cells (HT-29 and SW-620), a mouse model of colitis associated colorectal cancer and a murine model of xenograft tumor. The IC50values of 5-FU were 26.70±0.21μM in HT-29 cells and 26.71±2.06μM in SW-620 cells. Pretreatment with 0.05 or 0.1mM AOG down-regulated IC50values of 5-FU to 22.44±1.01 or 18.67±1.16μM in HT-29 and 21.21±1.49 or 17.99±1.42μM in SW-620 cells. AOG enhanced 5-FU-induced cell apoptosis and S phase arrest. The combination not only protected ICR mice against intestinal toxicities and carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate, but also decreased the xenograft tumor size, triggered apoptosis and inhibited proliferation of tumor cells in nude mice. The mechanisms of AOG on enhancing the growth inhibitory effect of 5-FU may be through the influence of TLR-4/NF-κB pathway. Taken together, the combinatorial therapy using AOG and 5-FU is a promising strategy for the treatment of colorectal cancer.
authors.affiliation: Laboratory of Oncological Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, PR China; No.422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, No. 210 Hospital of PLA, Liaoning 116000, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, PR China.
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Niu
authors.affiliation: No.422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Mian
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: No.422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xie
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address: ysun1145@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Oncological Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, PR China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address: qbmei53@hotmail.com.
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000009:adverse effects / Q000494:pharmacology*; D005685:Galactans / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007422:Intestines / Q000187:drug effects; D027845:Malus / Q000737:chemistry*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D005685:Galactans; D016328:NF-kappa B; D005472:Fluorouracil
keywords: 5-FU; An apple oligogalactan (AOG); Colorectal cancer (CRC)