title: CXCL9 attenuated chemotherapy-induced intestinal mucositis by inhibiting proliferation and reducing apoptosis.
abstract: Mucositis arising from cancer chemotherapy is a common problem for which there is no definitive treatment. 5-fluorouracil (5-FU) is a common cytotoxic agent used to treat solid tumors. A global gene expression array was performed to identify genetic signals involved in the pathogenesis of mucositis. The chemokine (C-X-C motif) ligand 9 (CXCL9) was one of the candidates identified that presented a characteristic gene expression profile; its temporal expression pattern was correlated with the damage and regeneration phases of the small intestine upon 5-FU chemotherapy. We found that prophylactic CXCL9 administration was able to attenuate the severity of mucositis, weight loss and diarrhea caused by chemotherapy. CXCL9 also increased the tolerance of the mice to lethal-dose chemotherapy. Moreover, we demonstrated that CXCL9 was able to promote the proliferation and regeneration of intestinal cells by inhibiting the proliferation of normal intestinal mucosal cells prior to chemotherapy and by reducing the 5-FU-induced apoptosis in intestinal crypts. Thus, pretreatment with CXCL9 is a new and promising strategy for the alleviation of chemotherapy-induced intestinal mucositis in clinical settings.
authors.affiliation: Department of surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, 600, Yishan Road, 200233 Shanghai, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
authors.forename: Zhenqian
authors.initials: Z
authors.lastname: Wu
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Di
authors.forename: Ye
authors.initials: Y
authors.lastname: Pan
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Yibao
authors.initials: Y
authors.lastname: Du
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Jin
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Pin
authors.initials: P
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054370:Chemokine CXCL9 / Q000494:pharmacology*; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D020869:Gene Expression Profiling; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052016:Mucositis / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D012720:Severity of Illness Index; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D054370:Chemokine CXCL9; D005472:Fluorouracil