Inhibition of Src tyrosine kinase on subcutaneously transplanted tumor of human lung adencarcinoma hi mice and its mechanism

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Author:
ZHENG Rui(2nd Department of Respiratory Internal Medicine, Shengjing Hospital, China Medical University, Shenyang 110022, China)
QIN Xiao-song()
LI Wen-jie(2nd Department of Respiratory Internal Medicine, Shengjing Hospital, China Medical University, Shenyang 110022, China)
WU Sha(2nd Department of Respiratory Internal Medicine, Shengjing Hospital, China Medical University, Shenyang 110022, China)
KANG Jian()
Journal Title:
CANCER RESEARCH AND CLINIC
Issue:
Volume 23, Issue 05, 2011
DOI:
10.3760/cma.j.issn.1006-9801.2011.05.004
Key Word:
Neoplasms, experimental;Lung neoplasms;Src family tyrosine kinase;Proliferation index;Microvessel density

Abstract: Objective To study the effect of Src tyrosine kinase inhibition on subcutaneously transplanted tumor of human lung adenocarcinoma in mice and its mechanism. Methods For the subcutaneously transplanted tumor model, A549 cells or PC-9 cells were inoculated into SCID mice by subcutaneous injection. Immunohistochemistry was used to show the effect of Src tyrosine kinase inhibition on proliferation index (Ki-67 staining) and microvessel density (CD31 staining) of subcutaneously transplanted tumor of human lung adenocarcinoma in mice. Results Subcutaneously transplanted tumor of PC-9 cells was sensitive to src tyrosine kinase inhibitor. There was significant difference between treatment group and control group (P <0.01). There was significant difference between the two treatment group too (P <0.01). Stopping treatment for 1 week, the inhibition rate of tumor growth were 33.19 % and 84.79 % in 10 mg·kg-1·d-1 and 50 mg·kg-1·d-1 treatment group, respectively. The same treatment was less effective to subcutaneous tumors produced by A549 cells. Treatment with 50 mg·kg-1·d-1 Src tyrosine kinase inhibitor significantly reduced the proliferation index of subcutaneously transplanted tumor produced by PC-9 cells (P<0.01) and tended to reduce the proliferation index of subcutaneously transplanted tumor produced by A549 cells (P >0.05). Treatment with 50 mg·kg-1·d-1 Src tyrosine kinase inhibitor significantly reduced micro vascular density in both PC-9 and A549 induced subcutaneous tumors (P <0.05). Conclusion Inhibition of Src tyrosine kinase could suppress the progression of subcutaneously transplanted tumor, not only by the inhibition of cell proliferation of lung adenocarcinoma cells directly, but also by the inhibition of angiogenesis indirectly.

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