Division of Otolaryngology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
Cancer Sci. 2013 Mar;104(3):369-74. doi: 10.1111/cas.12079. Epub 2013 Jan 30.
Cisplatin (CDDP) has been a key drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity is one of its adverse reactions that are dose limiting. To increase its antitumor effects and reduce such toxicity problems, polymeric micelles carrying CDDP (NC-6004) have been developed. The present study was designed to evaluate the efficacy and safety of NC-6004 for oral squamous cell carcinoma. In vitro antitumor activity was assayed in four oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of NC-6004, nude mice bearing OSC-19 were administered NC-6004 or CDDP. The in vitro growth-inhibitory effect of NC-6004 was significantly less than that of CDDP. However, both NC-6004 and CDDP showed equivalent antitumor effects in vivo. Mice with CDDP developed renal cell apoptosis; however, those injected with NC-6004 were almost free of renal cell injury. Moreover, in an orthotopic tongue cancer model using OSC-19, NC-6004 reduced the rate of sentinel lymph node metastasis to lower than that with CDDP. In conclusion, considering the potential advantages in terms of noticeable antitumor activity, lymphatic drug delivery and reduced nephrotoxicity, NC-6004 represents a significant structural improvement in the development of a platinum complex.
顺铂（CDDP）一直是头颈部鳞状细胞癌患者化疗的关键药物。肾毒性是其剂量限制的不良反应之一。为了提高其抗肿瘤效果并减少此类毒性问题，已经开发出携带顺铂的聚合物胶束（NC-6004）。本研究旨在评估 NC-6004 治疗口腔鳞状细胞癌的疗效和安全性。在四种口腔鳞状细胞癌细胞系中进行了体外抗肿瘤活性测定。为了研究 NC-6004 的抗肿瘤和肾毒性作用，将携带 OSC-19 的裸鼠给予 NC-6004 或 CDDP。NC-6004 的体外生长抑制作用明显小于 CDDP。然而，NC-6004 和 CDDP 在体内均显示出等效的抗肿瘤作用。用 CDDP 治疗的小鼠发生肾细胞凋亡；然而，注射 NC-6004 的小鼠几乎没有肾细胞损伤。此外，在使用 OSC-19 的原位舌癌模型中，NC-6004 将前哨淋巴结转移率降低到低于 CDDP 的水平。总之，考虑到在抗肿瘤活性、淋巴递药和降低肾毒性方面的潜在优势，NC-6004 代表了铂类复合物开发方面的重大结构改进。
