Τίτλος:
Combinatorial treatment of tinzaparin and chemotherapy can induce a significant antitumor effect in pancreatic cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Sarantis, P.
Bokas, A.
Papadimitropoulou, A.
Koustas, E.
Theocharis, S.
Papakotoulas, P.
Schizas, D.
Papalampros, A.
Felekouras, E.
Papavassiliou, A.G.
Karamouzis, M.V.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
gemcitabine; paclitaxel; tinzaparin; 130-nm albumin-bound paclitaxel; albuminoid; antineoplastic agent; Casp3 protein, mouse; caspase 3; deoxycytidine; gemcitabine; paclitaxel; tinzaparin, angiogenesis; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; Article; cancer combination chemotherapy; cell survival; controlled study; dose response; drug potentiation; human; human cell; in vitro study; in vivo study; mouse; NOD SCID mouse; nonhuman; pancreas cancer; survival time; tumor volume; animal; cell proliferation; drug effect; drug screening; gene expression regulation; metabolism; nonobese diabetic mouse; pancreas tumor; SCID mouse; tumor cell line, Albumins; Animals; Antineoplastic Combined Chemotherapy Protocols; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cell Survival; Deoxycytidine; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Paclitaxel; Pancreatic Neoplasms; Tinzaparin; Xenograft Model Antitumor Assays
DOI:
10.3390/ijms22137053
