Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors.
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.
Zhu
Li-Ping
LP
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
Yin
Yan
Y
Xing
Jing
J
Li
Chen
C
Kou
Lei
L
Hu
Bi
B
Wu
Zhi-Wei
ZW
Wang
Jian-Jun
JJ
Xu
Gen-Xing
GX
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
D043169:Endostatins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide
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