title: Medicinal facilities to B16F10 melanoma cells for distant metastasis control with a supramolecular complex by DEAE-dextran-MMA copolymer/paclitaxel.
abstract: The resistance of cancer cells to chemotherapeutic drugs (MDR) is a major problem to be solved. A supramolecular DEAE-dextran-MMA copolymer (DDMC)/paclitaxel (PTX) complex was obtained by using PTX as the guest and DDMC as the host having 50-300 nm in diameter. The drug resistance of B16F10 melanoma cells to paclitaxel was observed, but there is no drug resistance of melanoma cells to the DDMC/PTX complex in vitro. The cell death rate was determined using Michaelis-Menten kinetics, as the DDMC/PTX complex promoted allosteric supramolecular reaction to tubulin. The DDMC/PTX complex showed a very superior anti-cancer activity to paclitaxel alone in vivo. The median survival time (MST) of the saline, PTX, DDMC/PTX4 (particle size, 50 nm), and DDMC/PTX5 (particle size, 290 nm) groups were 120 h (T/C, 1.0), 176 h (T/C, 1.46), 328 h (T/C, 2.73), and 280 h (T/C, 2.33), respectively. The supramolecular DDMC/PTX complex showed the twofold effectiveness of PTX alone (p < 0.036). Histochemical analysis indicated that the administration of DDMC/PTX complex decreased distant metastasis and increased the survival of mice. A mouse of DDMC/PTX4 group in vivo was almost curing after small dermatorrhagia owing to its anti-angiogenesis, and it will be the hemorrhagic necrotic symptom of tumor by the release of "tumor necrosis factor alpha (TNF-α)" cytokine. As the result, the medicinal action of the DDMC/PTX complex will suppress the tumor-associated action of M2 macrophages and will control the metastasis of cancer cells.
authors: Department of Infectious Disease Control, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan, yeshita@oita-u.ac.jp.
authors: Yuki
authors: Y
authors: Eshita
authors: Rui-Cheng
authors: RC
authors: Ji
authors: Masayasu
authors: M
authors: Onishi
authors: Takashi
authors: T
authors: Kobayashi
authors: Masaaki
authors: M
authors: Mizuno
authors: Jun
authors: J
authors: Yoshida
authors: Naoji
authors: N
authors: Kubota
authors: Yasuhiko
authors: Y
authors: Onishi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D008768:Methylmethacrylates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D003911:Dextrans; D008768:Methylmethacrylates; C544087:diethylaminoethyl-dextran-methyl methacrylate graft copolymer; D017239:Paclitaxel