Sun Xu, Lou Li-Guang, Sui Dong-Hu, Wu Xiao-Hua
The Clinical Department, Guizhou Yibai Pharmaceutical Co.Ltd, Guiyang, China E-mail :
Asian Pac J Cancer Prev. 2014;15(22):9939-43. doi: 10.7314/apjcp.2014.15.22.9939.
Lobaplatin, one of the third-generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in-vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in-vitro antitumor activities were evaluated with cisplatin-sensitive and cisplatin-resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with IC50 values from 0.9 to 13.8 μmol/L in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum-sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum-resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.
洛铂是第三代铂类化合物之一，已在多种肿瘤类型中显示出令人鼓舞的抗癌活性。然而，洛铂在卵巢癌中的疗效尚未得到系统评估。在本研究中，对洛铂单药及其与紫杉烷联合用药进行了卵巢癌体外及体内模型研究。使用磺酰罗丹明B（SRB）法，将洛铂单药及其与紫杉烷联合用药的细胞毒性作用与顺铂和卡铂在七种卵巢癌细胞系中的作用进行了比较。此外，在裸鼠体内用人卵巢癌顺铂敏感和耐药异种移植瘤评估了体外抗肿瘤活性。洛铂的细胞毒性与顺铂和卡铂相似或更高，在多种卵巢癌细胞中的IC50值为0.9至13.8μmol/L。洛铂与多西他赛联合用药在体外产生了增强的细胞毒性活性。此外，在铂敏感的卵巢癌异种移植瘤中，洛铂单药显示出与顺铂和卡铂相似的抗肿瘤活性。此外，洛铂单药或与多西他赛联合用药在铂耐药的卵巢癌异种移植瘤中表现出显著活性。这些结果表明，单独使用洛铂或与多西他赛联合使用可能是一种合理且新颖的卵巢癌治疗策略。显然有必要对洛铂进行进一步的临床开发。
