Novel therapeutic potential in targeting microtubules by nanoparticle albumin-bound paclitaxel in hepatocellular carcinoma
Publication in refereed journal


摘要Hepatocellular carcinoma (HCC) shows low response to most conventional chemotherapies. To facilitate target identification for novel therapeutic development, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver, which is also considered as the pre-malignant liver lesion. In conjunction with ontology analysis, a major functional process found to play a role in the malignant transformation of HCC was inicrotubule-related cellular assembly. We further examined the potential use of microtubule targeting taxane drugs, including paclitaxel and docetaxel, and compared with findings to results from doxorubicin, a common chemotherapeutic agent used in HCC. 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 IC(50) dose at 15-fold lower than paclitaxel alone or the derivative analogue docetaxel, and similar to 450-fold less compared to doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G(2)/M phase and increased apoptosis following nob-paclitaxel treatment. In vivo animal studies also showed that nab-paclitaxel readily inhibited xenograft growth with less toxicity to host cells compared to other anti-microtubule drugs and doxorubicin. Gene silencing of the microtubule regulatory gene STMN1 by RNAi suggested a distinct synergistic effect in the combined treatment with nab-paclitaxel. Our findings in this study highly suggest that the microtubule assembly represents a promising therapeutic target development in HCC.
著者Zhou QA, Ching AKK, Leung WKC, Szeto CYY, Ho SM, Chan PKS, Yuan YF, Lai PBS, Yeo W, Wong N
期刊名稱International Journal of Oncology
頁次721 - 731
關鍵詞expression array; hepatocellular carcinoma; nab-paclitaxel; STMN1; therapy
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2021-20-09 於 23:41