A novel combretastatin A-4 derivative, AC-7700, shows marked antitumor activity against advanced solid tumors and orthotopically transplanted tumors
A novel combretastatin A-4 derivative, AC-7700, shows marked antitumor activity against advanced solid tumors and orthotopically transplanted tumors
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DOI：
10.1111/j.1349-7006.1999.tb00850.x
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发表时间：
1999-09-01
期刊：
影响因子：
--
通讯作者：
Tsuruo, T
中科院分区：
文献类型：
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作者：
Nihei, Y;Suga, Y;Tsuruo, T
AC-7700是一种新型的考布他汀A-4衍生物，通过抑制肿瘤灌注来抑制实体瘤的生长。我们在两种实验模型中评价了AC-7700对实体瘤的抗肿瘤活性，（鼠结肠26（c26）腺癌，结肠38（c38）腺癌，MethA纤维肉瘤，肉瘤180（S180），刘易斯肺癌（3LL），人LS 180腺癌）和原位移植肿瘤模型（c26）的最大耐受剂量（MTD）。当肿瘤体积（TV）达到0.2- 0.5cm后开始治疗时，CDDP的最大耐受剂量（MTD）抑制早期c26和c38肿瘤生长：但当TV超过2厘米时，它对处于晚期生长阶段的相同肿瘤的活性会降低（3）。在MTD时，AC-7700对除3LL外的所有受试肿瘤在早期和晚期生长阶段均具有活性，可减少肿瘤质量并对晚期c38肿瘤具有疗效，AC-7700对原位移植的c26肿瘤也有效，显示出与皮下肿瘤相当的活性。AC-7700通过诱导内源性肿瘤坏死因子-α的产生而破坏肿瘤血管系统，在无胸腺小鼠和正常胸腺小鼠中，AC-7700有效抑制晚期c26肿瘤的生长。这些结果表明，AC-7700是一种新型抗血管药物，在临床环境中可能对晚期癌症具有强效活性。
AC-7700, a novel combretastatin A-4 derivative, suppresses the growth of solid tumors by inhibiting tumor perfusion, We evaluated the antitumor activity of AC-7700 on solid tumors in two experimental models, an advanced tumor model (murine colon 26 (c26) adenocarcinoma, colon 38 (c38) adenocarcinoma, MethA fibrosarcoma, Sarcoma 180 (S180), Lewis lung carcinoma (3LL), human LS180 adenocarcinoma) and an orthotopically transplanted tumor model (c26), compared with that of cisplatin (CDDP), The maximum tolerable dose (MTD) of CDDP suppressed early-stage c26 and c38 tumor growth when treatment was started after the tumor volume (TV) reached 0.2-0.5 cm: but it showed reduced activity against the same tumors at an advanced growth stage when TV exceeded 2 cm(3). At its MTD, AC-7700 was active against all tumors tested except 3LL in both early and advanced growth stages, reducing the tumor mass and having a curative effect in advanced c38 tumors, AC-7700 was also effective on orthotopically transplanted c26 tumors, showing a comparable activity to that on subcutaneous tumors, Unlike flavon acetic acid, which damages tumor vasculature by inducing endogenous tumor necrosis factor-a production, AC-7700 potently suppressed the growth of advanced c26 tumors in athymic as well as euthymic mice. These results suggest that AC-7700 is a novel antivascular agent that may have potent activity against advanced-stage cancer in the clinical setting.