Abstract 4423: Novel therapeutic potential in targeting the microtubules by nanoparticle albumin-bound paclitaxel in hepatocellular carcinoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.4423-4423
• Main Authors: Zhou, Qian, Ching, Arthur K-K, Leung, Wilson K-C, Szeto, Carol, Ho, Shuk-Mei, Holmes, Chris C., Yuan, Yun-fei, Lai, Paul B-S, Yeo, Winnie, Wong, Nathalie
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-4423

Hepatocellular carcinoma (HCC) shows low responses to most conventional chemotherapies. To facilitate target identifications for novel therapeutic developments, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver. Coupled with ontology analysis, the major functional process suggested in the malignant transformation of HCC was microtubule-related cellular assembly. We further examined the potential use of microtubule targeting Taxane drugs, including Paclitaxel and Docetaxel, and compared findings to the results obtained from Doxorubicin, a common chemotherapeutic agent used in the treatment of a number of neoplasms. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, the nanoparticle albumin-bound (nab)-Paclitaxel was also examined. In a panel of HCC cell lines studied, a high sensitivity towards Taxane drugs was generally found, although the effect from nab-Paclitaxel was most profound. The nab-Paclitaxel showed an effective IC50 dose at 15-fold lower than Paclitaxel alone or the derivative analogue Docetaxel, and approx.450-fold less compared to Doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G2/M phase and increased apoptosis following treatment with nab-Paclitaxel. In-vivo animal study also showed that nab-Paclitaxel readily inhibited xenograft growth with less toxicity compared to other anti-microtubule drugs and Doxorubicin. Silencing of a major microtubule regulatory gene STMN1 suggested a distinct synergistic effect in the combined treatment with nab-Paclitaxel. Our findings in this study would suggest the microtubule organizations to represent a promising target for treatment developments in HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4423.