Nab-paclitaxel is effective against intrahepatic cholangiocarcinoma via disruption of desmoplastic stroma

Peter Mu Hsin Chang, Chi Tung Cheng, Ren Chin Wu, Yi Hsiu Chung, Kun Chun Chiang, Ta Sen Yeh, Chun Yu Liu, Ming Han Chen, Ming Huang Chen*, Chun Nan Yeh

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

Intrahepatic cholangiocarcinoma (IH-CCA) is the second predominant hepatic malignancy worldwide. However, effective treatment strategies for IH-CCA have not yet been developed. Nab-paclitaxel may be an effective drug against IH-CCA, a type of desmoid-like tumor, and its antitumor effects may be attributable to its ability to disrupt the cancer-associated fibroblasts. In the present study, MTT and Annexin-V apoptosis detection kits were used to evaluate the efficacy of paclitaxel and nab-paclitaxel against human cholangiocarcinoma KKU-100 and KKU-213 cell lines. A rat model of thioacetamide-induced spontaneous desmoplastic IH-CCA was used to compare the treatment response of four different drug regimens: Control, paclitaxel, nab-paclitaxel and gemcitabine/oxaliplatin. Positron emission tomography and immunofluorescence analysis were used to measure the tumor volume and to study the resected tumor, respectively. In vitro, paclitaxel and nab-paclitaxel induced anti-proliferative effects in KKU-100 and KKU-M213 cells. With regards to the treatment regimes, only nab-paclitaxel and gemcitabine/oxaliplatin induced antitumor effects in the rat model of thioacetamide-induced IH-CCA. The immunofluorescence study indicated that nab-paclitaxel was more efficient in disrupting cancer-associated fibroblasts than paclitaxel. In conclusion, nab-paclitaxel is effective against IH-CCA owing to its ability to markedly disrupt the desmoplastic stroma.

Original languageEnglish
Pages (from-to)566-572
Number of pages7
JournalOncology Letters
Volume16
Issue number1
DOIs
StatePublished - 07 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018, Spandidos Publications. All rights reserved.

Keywords

  • Cancer-associated fibroblast
  • Cholangiocarcinoma
  • Desmoplastic
  • Nab-paclitaxel
  • α-smooth muscle actin

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