Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma

Carlotta Borsoi; Fransisca Leonard; Yeonju Lee; Mohamed Zaid; Dalia Elganainy; Jenolyn Francisca Alexander; Megumi Kai; Yan Ting Liu; Yaan Kang; Xuewu Liu; Eugene J. Koay; Mauro Ferrari; Biana Godin; Kenji Yokoi

doi:10.1016/j.canlet.2017.06.026

Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma

Carlotta Borsoi, Fransisca Leonard, Yeonju Lee, Mohamed Zaid, Dalia Elganainy, Jenolyn Francisca Alexander, Megumi Kai, Yan Ting Liu, Yaan Kang, Xuewu Liu, Eugene J. Koay, Mauro Ferrari, Biana Godin, Kenji Yokoi

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The mechanism for improved therapeutic efficacy of the combination therapy with nanoparticle albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant human PDAC in which increasing gem transport would not improve the efficacy, thus revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic outcomes and transport of nAb-PTX to PDAC as a result of (1) encapsulating nAb-PTX in multistage nanovectors (MSV); (2) effect of gem on caveolin-1 expression. Treatment with MSV/nAb-PTX + gem was highly efficient in prolonging animal survival in comparison to other therapeutic regimens. MSV/nAb-PTX + gem also caused a substantial increase in tumor PTX accumulation, significantly reduced tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that nAb-PTX treatment of gem-resistant PDAC can be enhanced by (1) gem through up-regulation of caveolin-1 and (2) MSV through increasing accumulation of nAb-PTX in the tumor.

Original language	English (US)
Pages (from-to)	296-304
Number of pages	9
Journal	Cancer Letters
Volume	403
DOIs	https://doi.org/10.1016/j.canlet.2017.06.026
State	Published - Sep 10 2017

Keywords

Drug resistance
Gemcitabine
Multistage nanovectors
Pancreatic cancer
Transport
nAb-paclitaxel

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.canlet.2017.06.026

Cite this

Borsoi, C., Leonard, F., Lee, Y., Zaid, M., Elganainy, D., Alexander, J. F., Kai, M., Liu, Y. T., Kang, Y., Liu, X., Koay, E. J., Ferrari, M., Godin, B., & Yokoi, K. (2017). Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma. Cancer Letters, 403, 296-304. https://doi.org/10.1016/j.canlet.2017.06.026

@article{aa22df5b15f443988b8d70da787d6db2,

title = "Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma",

abstract = "The mechanism for improved therapeutic efficacy of the combination therapy with nanoparticle albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant human PDAC in which increasing gem transport would not improve the efficacy, thus revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic outcomes and transport of nAb-PTX to PDAC as a result of (1) encapsulating nAb-PTX in multistage nanovectors (MSV); (2) effect of gem on caveolin-1 expression. Treatment with MSV/nAb-PTX + gem was highly efficient in prolonging animal survival in comparison to other therapeutic regimens. MSV/nAb-PTX + gem also caused a substantial increase in tumor PTX accumulation, significantly reduced tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that nAb-PTX treatment of gem-resistant PDAC can be enhanced by (1) gem through up-regulation of caveolin-1 and (2) MSV through increasing accumulation of nAb-PTX in the tumor.",

keywords = "Drug resistance, Gemcitabine, Multistage nanovectors, Pancreatic cancer, Transport, nAb-paclitaxel",

author = "Carlotta Borsoi and Fransisca Leonard and Yeonju Lee and Mohamed Zaid and Dalia Elganainy and Alexander, {Jenolyn Francisca} and Megumi Kai and Liu, {Yan Ting} and Yaan Kang and Xuewu Liu and Koay, {Eugene J.} and Mauro Ferrari and Biana Godin and Kenji Yokoi",

note = "Funding Information: This work was supported by the National Cancer Institute (NCI 1-U54-CA143837); the National Institutes of Health (NIH 1-U54-CA151668-01). M. Ferrari would like to acknowledge support via the Ernest Cockrell Jr. Presidential Distinguished Chair. E. Koay would like to acknowledge support from MD Anderson Cancer Center including the Cancer Moonshots program and the Center for Advanced Biomedical Imaging with equipment support from GE Healthcare. The funding sources had no involvement in the conduct of the research and/or the preparation of the manuscript. Publisher Copyright: {\textcopyright} 2017 Elsevier B.V.",

year = "2017",

month = sep,

day = "10",

doi = "10.1016/j.canlet.2017.06.026",

language = "English (US)",

volume = "403",

pages = "296--304",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma

AU - Borsoi, Carlotta

AU - Leonard, Fransisca

AU - Lee, Yeonju

AU - Zaid, Mohamed

AU - Elganainy, Dalia

AU - Alexander, Jenolyn Francisca

AU - Kai, Megumi

AU - Liu, Yan Ting

AU - Kang, Yaan

AU - Liu, Xuewu

AU - Koay, Eugene J.

AU - Ferrari, Mauro

AU - Godin, Biana

AU - Yokoi, Kenji

N1 - Funding Information: This work was supported by the National Cancer Institute (NCI 1-U54-CA143837); the National Institutes of Health (NIH 1-U54-CA151668-01). M. Ferrari would like to acknowledge support via the Ernest Cockrell Jr. Presidential Distinguished Chair. E. Koay would like to acknowledge support from MD Anderson Cancer Center including the Cancer Moonshots program and the Center for Advanced Biomedical Imaging with equipment support from GE Healthcare. The funding sources had no involvement in the conduct of the research and/or the preparation of the manuscript. Publisher Copyright: © 2017 Elsevier B.V.

PY - 2017/9/10

Y1 - 2017/9/10

N2 - The mechanism for improved therapeutic efficacy of the combination therapy with nanoparticle albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant human PDAC in which increasing gem transport would not improve the efficacy, thus revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic outcomes and transport of nAb-PTX to PDAC as a result of (1) encapsulating nAb-PTX in multistage nanovectors (MSV); (2) effect of gem on caveolin-1 expression. Treatment with MSV/nAb-PTX + gem was highly efficient in prolonging animal survival in comparison to other therapeutic regimens. MSV/nAb-PTX + gem also caused a substantial increase in tumor PTX accumulation, significantly reduced tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that nAb-PTX treatment of gem-resistant PDAC can be enhanced by (1) gem through up-regulation of caveolin-1 and (2) MSV through increasing accumulation of nAb-PTX in the tumor.

AB - The mechanism for improved therapeutic efficacy of the combination therapy with nanoparticle albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant human PDAC in which increasing gem transport would not improve the efficacy, thus revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic outcomes and transport of nAb-PTX to PDAC as a result of (1) encapsulating nAb-PTX in multistage nanovectors (MSV); (2) effect of gem on caveolin-1 expression. Treatment with MSV/nAb-PTX + gem was highly efficient in prolonging animal survival in comparison to other therapeutic regimens. MSV/nAb-PTX + gem also caused a substantial increase in tumor PTX accumulation, significantly reduced tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that nAb-PTX treatment of gem-resistant PDAC can be enhanced by (1) gem through up-regulation of caveolin-1 and (2) MSV through increasing accumulation of nAb-PTX in the tumor.

KW - Drug resistance

KW - Gemcitabine

KW - Multistage nanovectors

KW - Pancreatic cancer

KW - Transport

KW - nAb-paclitaxel

UR - http://www.scopus.com/inward/record.url?scp=85023642175&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023642175&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2017.06.026

DO - 10.1016/j.canlet.2017.06.026

M3 - Article

C2 - 28687352

AN - SCOPUS:85023642175

SN - 0304-3835

VL - 403

SP - 296

EP - 304

JO - Cancer Letters

JF - Cancer Letters

ER -

Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this