Among the many biological characteristics of cancer, matrix-metalloproteinases (MMPs) are essential for tumor invasion and metastasis. To test the possibility of ex vivo model as a therapeutic guideline for MMP inhibitor (MMPI) treatment, we evaluated IC50 of the gabexate mesylate against MMP-9. Thirty-four paired normal and gastric cancer tissues were tested to measure the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography. Both MMP-9 expression (p=0.04) and IC50 (p=0.02) were higher in cancer than normal tissues. IC50 of the cancer tissues was higher than paired normal tissues especially in cases with large tumor (greater than or equal to5 cm) (p=0.03), higher T-stage (p=0.04), lymph node metastasis (p=0.04) and advanced stage (p=0.04). In cancers extending beyond submucosa or in diffuse/mixed type, a tendency of higher IC50 was observed than tumors confined to submucosa or intestinal type cancer despite similar MMP-9 activity between the groups. Patients with high IC50 showed poorer prognosis than patients with low IC50 in curatively-resected group. In multivariate analysis, high IC50 was suggested as an independent prognostic factor. We were able to differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who may benefit from MMPI treatment.
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Nanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R ChinaNanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R China
Ye, Teng
Ye, Fangfu
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Chinese Acad Sci, Inst Phys, Beijing Natl Lab Condensed Matter Phys, Beijing 100190, Peoples R China
Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325001, Peoples R ChinaNanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R China
Ye, Fangfu
Qiu, Feng
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Nanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R China
Nanchang Univ, Affiliated Hosp 1, Dept Oncol, Nanchang 330006, Jiangxi, Peoples R ChinaNanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R China
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First Clinical Medical College,Nanchang UniversityFirst Clinical Medical College,Nanchang University
叶腾
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叶方富
邱峰
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First Clinical Medical College,Nanchang University
Department of Oncology,First Affiliated Hospital of Nanchang UniversityFirst Clinical Medical College,Nanchang University