Cancer lettersJul 9, 2017

Gemcitabine helps deliver albumin-bound paclitaxel nanoparticles in gemcitabine-resistant pancreatic cancer

Updated Mar 3, 2026

Abstract

Treatment with multistage nanovectors and nanoparticle albumin-bound paclitaxel plus gemcitabine significantly prolonged survival in mice with gem-resistant pancreatic cancer.

Combination therapy resulted in a substantial increase in tumor accumulation of paclitaxel.
The therapy significantly reduced tumor growth and cell proliferation while increasing apoptosis in tumor cells.
Gemcitabine was found to enhance caveolin-1 expression, which is associated with improved transport of paclitaxel to the tumor.
Findings were corroborated by patient data from those who received gemcitabine-based neo-adjuvant chemotherapy.

Simplified

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.

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Authors’ contributions . Conception and design: C. Borsoi, M. Ferrari, B. Godin, K. Yokoi. Development of methodology: C. Borsoi, X. Liu, B. Godin, K. Yokoi. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): C. Borsoi, F. Leonard, Y.T. Liu, X. Liu, J.F. Alexander, M Kai, Y Lee, M. Zaid, D. Elganainy, Y. Kang, E. Koay, B. Godin, K. Yokoi. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): C. Borsoi, Y. Lee, M. Zaid, D. Elganainy, E. Koay, M. Ferrari, B. Godin, K. Yokoi. Writing, review, and/or revision of the manuscript: C. Borsoi, Y. Lee, M. Zaid, D. Elganainy, E. Koay, M. Ferrari, B. Godin, K. Yokoi. Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): C. Borsoi, B. Godin, K. Yokoi. Study supervision: B. Godin, K. Yokoi. Conflicts of interest . M. Ferrari is the founding scientist and a member of the Board of Directors of NanoMedical Systems, and a member of Board of Directors of Arrowhead Research Corporation, and hereby discloses potential financial interests in the companies. No potential conflicts of interest were disclosed by the other authors.

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