Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol®-resistant ovarian cancer

Yao An Shen, Wai Hou Li, Po Hung Chen, Chun Lin He, Yen Hou Chang, Chi Mu Chuang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Taxol® remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resis-tant cell line (TR) was established at frst. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol® versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol® (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

Original languageEnglish
Pages (from-to)841-855
Number of pages15
JournalAmerican Journal of Translational Research
Volume7
Issue number5
Publication statusPublished - Jul 7 2015
Externally publishedYes

Fingerprint

Neoplastic Stem Cells
Paclitaxel
Stem cells
Liposomes
Ovarian Neoplasms
Tumors
Neoplasms
Metabolism
Stomach Neoplasms
Therapeutics
Pharmaceutical Preparations
Nanomedicine
Medical nanotechnology
Recurrence
Translational Medical Research
Oxidative Phosphorylation
Peritoneal Cavity
Glycolysis
Growth
Pancreatic Neoplasms

Keywords

  • Cancer stem cell
  • Epithelial-mesenchymal transition
  • Liposome
  • Metabolic reprogram-ming
  • P53
  • Stemness

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

Cite this

Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol®-resistant ovarian cancer. / Shen, Yao An; Li, Wai Hou; Chen, Po Hung; He, Chun Lin; Chang, Yen Hou; Chuang, Chi Mu.

In: American Journal of Translational Research, Vol. 7, No. 5, 07.07.2015, p. 841-855.

Research output: Contribution to journalArticle

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