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SUPPRESSION OF TUMOR GROWTH BY ANTIANGIOGENIC AGENT AND INDUCTION TO TUMOR DORMANCY IN BREAST CANCER

乳腺癌中抗血管生成剂抑制肿瘤生长并诱导肿瘤休眠

基本信息

批准号：
12671139
负责人：
HORIGUCHI Jun
金额：
$ 1.34万
依托单位：
GUNMA UNIVERSITY FACULTY OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671139/
关键词：
ANTIANGIOGENIC AGENT TNP-470 APOPTOSIS MDA-MB-231 TUMOR UFT VEGF TAMOXIFEN DORMANCY THERAPY 血管新生 MDA-MB-231 乳癌 Vascular endothelial growth factor Apoptosis 5-fluorouracil

项目摘要

Angiogenesis is one of the key mechanisms of tumor development, invasion and metastasis. Suppression of tumor growth by antiangiogenic agent (TNP-470) is induced by apoptosis of cancer cells. Combination therapy of TNP-470 with UFT suppressed growth of MDA-MB-231 tumor compared to TNP-470 alone. The 5-FU concentration was higher in MDA-MB-231 tumors treated by TNP-470 plus UFT than TNP-470 alone. It was suggested that TNP-470 might increase 5-FU concentration in MDA-MB-231 tumors. Suppression of tumor growth by combination therapy of UFT with TNP-470 may be owing to the increase of 5-FU in the tumors. VEGF is one of growth factors with strong angiogenesis. VEGF production in cancer cells is suppressed by some chemo- and/or endocrine therapy. Tamoxifen inhibited VEGF production of ER-positive MCF-7 cells. Similarly, combination therapy of UFT with TNP-470 decreased VEGF concentration in MDA-MB-231 tumors. VEGF production was not suppressed by TNP-470 alone. Combination therapy of UFT with TNP-470 inhibited VEGF production of MDA-MB-231 tumors, which might be induced by increase of intra-tumoral concentration of 5-FU. Combination therapy of chemo-endocrine and antiangiogenic agents may induce breast cancer to tumor dormancy.

血管生成是肿瘤发生、侵袭和转移的重要机制之一。抗血管生成剂（TNP-470）对肿瘤生长的抑制作用是由肿瘤细胞凋亡诱导的。与单独使用TNP-470相比，TNP-470联合UFT治疗可抑制MDA-MB-231肿瘤的生长。tnf -470联合UFT治疗的MDA-MB-231肿瘤中5-FU浓度高于单独tnf -470。提示TNP-470可能增加MDA-MB-231肿瘤中5-FU的浓度。UFT联合TNP-470抑制肿瘤生长可能是由于肿瘤中5-FU的增加。VEGF是一种具有较强血管生成能力的生长因子。一些化疗和/或内分泌治疗可抑制癌细胞中VEGF的产生。他莫昔芬抑制er阳性MCF-7细胞的VEGF生成。同样，UFT与TNP-470联合治疗可降低MDA-MB-231肿瘤中的VEGF浓度。tnf -470未单独抑制VEGF的产生。UFT联合TNP-470治疗可抑制MDA-MB-231肿瘤中VEGF的产生，这可能与肿瘤内5-FU浓度升高有关。化疗-内分泌联合抗血管生成药物可诱导乳腺癌进入肿瘤休眠。