Original Article
Docetaxel-polymeric nanoparticle enhances radiotherapeutic efficacy in human pancreatic cancer
Abstract
Background: Nanoparticle therapeutics is promising platform for cancer treatment. In our previous study, we have developed polymeric nanoparticles (PNP) in which docetaxel was incorporated to reduce the side effects and improve the therapeutic efficacy, and recently finished its phase 1 clinical study in patients with solid tumors.
Methods: Radiotherapeutic efficacy of the docetaxel-contained PNP (DTX-PNP) in pancreatic cancer cells was determined by both in vitro and in vivo assay such as clonogenic survival assay with cancer cell lines, western blot for apoptotic cell death and tumor growth inhibition assay using several kinds of xenograft models. The tumors derived from human pancreatic cancer AsPC-1 or BxPC-3 cells were analyzed by immunohistochemistry (IHC) to detect in apoptosis and tubulin polymerization induced by DTX-PNP. The combinational therapeutic effect of DTX-PNP and ionizing radiation (IR) was evaluated in vivo mice models of AsPC-1 or BxPC-3 cell line-derived xenograft models and patient-derived xenograft model, and compared to that of reference drugs.
Results: DTX-PNP in combination with IR showed high cytotoxicity to pancreatic cancer cells, and ultimate inhibition of cell proliferation as determined via in vitro assays. In vivo radiotherapeutic efficacy was markedly enhanced by intravenous injection of DTX-PNP comparing to Gemzar, a common chemoradiation therapeutic agent in pancreatic cancer.
Conclusions: These results suggested DTX-PNP can hold an invaluable and promising position in treating human pancreatic cancer as a novel and effective radiosensitizing agent.
Methods: Radiotherapeutic efficacy of the docetaxel-contained PNP (DTX-PNP) in pancreatic cancer cells was determined by both in vitro and in vivo assay such as clonogenic survival assay with cancer cell lines, western blot for apoptotic cell death and tumor growth inhibition assay using several kinds of xenograft models. The tumors derived from human pancreatic cancer AsPC-1 or BxPC-3 cells were analyzed by immunohistochemistry (IHC) to detect in apoptosis and tubulin polymerization induced by DTX-PNP. The combinational therapeutic effect of DTX-PNP and ionizing radiation (IR) was evaluated in vivo mice models of AsPC-1 or BxPC-3 cell line-derived xenograft models and patient-derived xenograft model, and compared to that of reference drugs.
Results: DTX-PNP in combination with IR showed high cytotoxicity to pancreatic cancer cells, and ultimate inhibition of cell proliferation as determined via in vitro assays. In vivo radiotherapeutic efficacy was markedly enhanced by intravenous injection of DTX-PNP comparing to Gemzar, a common chemoradiation therapeutic agent in pancreatic cancer.
Conclusions: These results suggested DTX-PNP can hold an invaluable and promising position in treating human pancreatic cancer as a novel and effective radiosensitizing agent.
