RESUMO
BACKGROUND: The gastric cancer is the second most malignant tumor in the world. HER-2 is one of the key targets for the gastric cancer therapy. Anti-HER-2 antibodies like trastuzumab, exhibits the satisfactory therapeutic effect in clinical. However, the drug resistance problem limits its application. METHOD: In this study, we develop a gold nanoshell (Gold Nanoshell) drug carrier for delivery and selective photo-thermal release of genes which target HER-2 and immunologic adjuvant CPG sequence in gastric tumor cells. The drug delivery system generated a multidimensional treatment strategy which includes gene-, immune- and photothermal-therapy. RESULTS: The whole gold nanoshell drug delivery system exhibits the well gene transduction ability and combined treatment effect. Both in vitro and in vivo results demonstrate the multiple therapeutic effects of the drug delivery system is better than the monotherapy. CONCLUSIONS: This study indicates the multiple combined therapy based on the gold nanoshell system would be a promising translational treatment for gastric cancer.
Assuntos
Ouro/química , Nanoconchas/química , Neoplasias Gástricas/terapia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Terapia Genética , Humanos , Hipertermia Induzida , Imunoterapia , Camundongos Nus , Terapia de Alvo Molecular , Fototerapia , Receptor ErbB-2/genética , Receptor ErbB-2/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologiaRESUMO
Low dose irradiation (LDIR) induces hormesis and adaptive response in organism and mammalian cell lines. Notably, LDIR generates distinct biological effects in cancer cells from normal cells, e.g., it may affect the growth of cancer cells via the activation of certain cell signaling pathway, which does not exist in normal cells. Therefore, LDIR is considered as a promising assistant method of clinical cancer therapy. In this study, we chose human colorectal adenocarcinoma cell line HT-29 as the experimental model, and investigated the differential biological effects between 250 mGy single dose LDIR and 250 mGy intermittent LDIR pretreatments in high dose irradiation (HDIR) radiotherapy and 5-fluorouracil (5-FU) based chemotherapy. Through the cell growth assays, we observed that 250 mGy intermittent LDIR pretreatment significantly increased the killing effect of both radiotherapy and chemotherapy. Western blotting results showed that intermittent LDIR pretreatment apparently activated the ATM/p53 (ataxia telangiectasia mutated, ATM) pathway in radiotherapy; it also activated ERK and p38MAPK pathways in chemotherapy. When we used chemical inhibitors to block the ATM/p53 or p38MAPK pathways, the intermittent LDIR induced cell growth inhibitions were reversed. However, blockage of ERK pathway could not affect the cell growth inhibiton in chemotherapy. Taken together, our findings evaluated the intermittent LDIR as a potential valuable method that can enhance the effectiveness of radiotherapy and chemotherapy, especially in the radio- or chemo-resistant tumor types.