Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Pavillon 3, Av, de Beaumont, 1011 Lausanne, Switzerland.
Mol Cancer. 2011 Jul 26;10:90. doi: 10.1186/1476-4598-10-90.
Targeted therapies for metastatic renal cell carcinoma (RCC), including mammalian target of rapamycin (mTOR) inhibitors and small-molecule multikinase inhibitors, have produced clinical effects. However, most patients acquire resistance over time. Thus, new therapeutic strategies need to be developed. Here, we evaluated the effect of the dual PI3K/mTOR inhibitor NVP-BEZ235, in combination with the multikinase inhibitor sorafenib on renal cancer cell proliferation and survival in vitro as well as on tumor growth in vivo.
The renal carcinoma cell lines 786-0 and Caki-1 were treated with NVP-BEZ235 or sorafenib, either alone or in combination. Tumor cell proliferation and apoptosis were investigated in vitro. The anticancer efficacy of NVP-BEZ235 alone, or in combination with sorafenib, was also evaluated on RCC xenografts in nude mice.
Treatment of 786-0 and Caki-1 cells with NVP-BEZ235 or sorafenib resulted in reduced tumor cell proliferation and increased tumor cell apoptosis in vitro. The combination of NVP-BEZ235 and sorafenib was more effective than each compound alone. Similarly, in vivo, NVP-BEZ235 or sorafenib reduced the growth of xenografts generated from 786-0 or Caki-1 cells. The antitumor efficacy of NVP-BEZ235 in combination with sorafenib was superior to NVP-BEZ235 or sorafenib alone.
Our findings indicate that the simultaneous use of NVP-BEZ235 and sorafenib has greater antitumor benefit compared to either drug alone and thus provides a treatment strategy in RCC.
针对转移性肾细胞癌（RCC）的靶向治疗，包括哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂和小分子多激酶抑制剂，已产生临床效果。然而，大多数患者随着时间的推移会产生耐药性。因此，需要开发新的治疗策略。在这里，我们评估了双重 PI3K/mTOR 抑制剂 NVP-BEZ235 与多激酶抑制剂索拉非尼联合应用对体外肾癌细胞增殖和存活以及体内肿瘤生长的影响。
用 NVP-BEZ235 或索拉非尼单独或联合处理肾癌细胞系 786-0 和 Caki-1。在体外研究肿瘤细胞增殖和凋亡。还在裸鼠 RCC 异种移植模型中评估了 NVP-BEZ235 单独或与索拉非尼联合的抗癌疗效。
NVP-BEZ235 或索拉非尼处理 786-0 和 Caki-1 细胞导致体外肿瘤细胞增殖减少和肿瘤细胞凋亡增加。NVP-BEZ235 与索拉非尼联合使用比单独使用每种化合物更有效。同样，在体内，NVP-BEZ235 或索拉非尼减少了源自 786-0 或 Caki-1 细胞的异种移植瘤的生长。NVP-BEZ235 与索拉非尼联合使用的抗肿瘤疗效优于 NVP-BEZ235 或索拉非尼单独使用。
我们的研究结果表明，与单独使用任何一种药物相比，同时使用 NVP-BEZ235 和索拉非尼具有更大的抗肿瘤益处，因此为 RCC 提供了一种治疗策略。
