title: Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors.
abstract: Granulocyte colony-stimulating factor (GCSF) is frequently used as an adjunctive agent in tumor chemotherapy. Bifidobacterium longums (B. longum) attracted researchers' interests due to its enhancement of immunity and selective location in solid tumors. B. longum-pBV22210-endostatin (Endo) was proved to have a definite inhibitive effect on tumor growth in our previous study. In the present study, we evaluated the effects of B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with cyclophosphamide (CTX) on H22 and S180 tumor-bearing mice. Based on our previous work, the plasmid pBV22210-GCSF was constructed and transformed by electroporation into B. longum. The B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with CTX were applied to treat H22 and S180 tumor-bearing mice. A leukocyte count was carried out and the tumor inhibition rate was calculated after treatment. In our study, CTX combined with B. longum-pBV22210-GCSF significantly raised the leukocyte level of tumor-bearing mice, while combined with B. longum-pBV22210-GCSF alone or B. longum-pBV22210-Endo alone combinations with CTX inhibited tumor growth by over 65%. The results showed that B. longum-pBV22210-GCSF had an effective antagonistic effect on bone marrow inhibited by CTX and could inhibit tumor growth when it was combined with B. longum-pBV22210-Endo and CTX. Our results provide an enhanced understanding of B. longum and GCSF as well as their potential as an adjunctive approach in cancer gene therapy.
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jiangsu Research Center for Gene Pharmaceutical Engineering and Technology, Suzhou, China. zlp04496117@yahoo.com.cn
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Xing
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Kou
authors.forename: Bi
authors.initials: B
authors.lastname: Hu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
authors.forename: Gen-Xing
authors.initials: GX
authors.lastname: Xu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001644:Bifidobacterium / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation; D043169:Endostatins / Q000008:administration & dosage / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D043169:Endostatins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide
references.citation: Hum Pathol. 1975 Nov;6(6):693-709
references.pmid: 1183993
references.citation: Appl Environ Microbiol. 2006 Jan;72(1):527-35
references.pmid: 16391088
references.citation: Cancer Gene Ther. 2007 Feb;14(2):151-7
references.pmid: 17068487
references.citation: Breast Cancer Res Treat. 2001 Mar;66(2):165-70
references.pmid: 11437103
references.citation: Cancer Gene Ther. 2000 Feb;7(2):269-74
references.pmid: 10770636
references.citation: Acta Haematol. 2001;105(3):151-5
references.pmid: 11463988
references.citation: Curr Oncol Rep. 2001 Mar;3(2):131-40
references.pmid: 11177745
references.citation: Nat Med. 1997 Feb;3(2):177-82
references.pmid: 9018236
references.citation: Eur J Cancer. 1995;31A(3):302-7
references.pmid: 7540401
references.citation: Nature. 1997 Nov 27;390(6658):404-7
references.pmid: 9389480
references.citation: Cell. 1997 Jan 24;88(2):277-85
references.pmid: 9008168
references.citation: J Dairy Sci. 1991 Apr;74(4):1187-95
references.pmid: 1860970
references.citation: Biotechnol Lett. 2007 Aug;29(8):1249-53
references.pmid: 17487549
references.citation: J Clin Oncol. 2002 Sep 15;20(18):3772-84
references.pmid: 12228197
references.citation: Cancer Gene Ther. 2003 Feb;10(2):105-11
references.pmid: 12536198
references.citation: Plasmid. 2008 Sep;60(2):136-48
references.pmid: 18652842
references.citation: Cancer Res. 1997 Oct 15;57(20):4537-44
references.pmid: 9377566
references.citation: Biotechnol Lett. 2008 Jan;30(1):165-72
references.pmid: 17849088
references.citation: Cancer Sci. 2006 Jul;97(7):649-57
references.pmid: 16827806
references.citation: Plasmid. 1994 Sep;32(2):208-11
references.pmid: 7846144
references.citation: J Dairy Sci. 2001 Jul;84(7):1583-9
references.pmid: 11467806
references.citation: J Clin Oncol. 2002 Sep 15;20(18):3792-803
references.pmid: 12228199
references.citation: Cancer Res. 1980 Jun;40(6):2061-8
references.pmid: 6989495
references.citation: Clin Cancer Res. 2001 Nov;7(11):3366-74
references.pmid: 11705849
references.citation: Nat Rev Cancer. 2004 Jun;4(6):437-47
references.pmid: 15170446
references.citation: Cancer Res. 1998 Apr 1;58(7):1408-16
references.pmid: 9537241
references.citation: FEMS Microbiol Rev. 1995 Oct;17(3):357-64
references.pmid: 7576773
references.citation: Blood. 1996 Sep 15;88(6):1907-29
references.pmid: 8822908
references.citation: Cancer Gene Ther. 2005 Feb;12(2):133-40
references.pmid: 15565182