geranylgeranylacetone and Lung-Neoplasms

Hsp90 is a major molecular chaperone, which overexpression is involved in oncogenesis, development and drug resistance in many human cancers. The aim of this study is to investigate the relationship between the GGA-induced overexpression of Hsp90 and chemoresistance to Cisplatin in SPCA-1 and H446 cell line.. The protein expressions of Hsp90 induced by GGA at different concentrations were analyzed by Immunofluorescence and Western blotting. Cells survival to Cisplatin was determined using the MTT assays. The effect of Hsp90 expression on the drug resistance to Cisplatin in two Cell Lines was analyzed.. Compared with the respective control cells, Hsp90 expressions in both experimental cell lines were up-regulated obviously, exhibiting a dose-dependent manner to GGA. MTT assays revealed that the IC50s of cisplatin also showed a substantial elevation for the experimental cells of SPCA-1 and H446, and this elevation was also associated with GGA concerntration.. GGA is effective for the induction of Hsp90 in the SPCA-1 and H446 cell line. Up-regulated Hsp90 is associated with the chemoresistance to Cisplatin in SPCA-1and H446 cells.

Topics: Cell Line, Tumor; Cell Survival; Cisplatin; Diterpenes; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Up-Regulation

We examined whether hyperthermia attenuated the metastatic potential of colon cancer through the induction of heat shock protein 70 (Hsp70).. Colon26 cells were separated into four groups: (1) no pretreatment, (2) hyperthermia at 42 degrees C for 1 hour, (3) pretreatment with geranylgeranylacetone (GGA) 10(-6) M for 2 hours, and (4) hyperthermia after GGA treatment. We measured cell viabilities and the contents of Hsp70. We assessed nuclear factor-kappa-B (NF-kappa-B) status with and without tumor necrosis factor-alpha (TNF-alpha) stimulation. For in vivo study, colon26 cells were injected via the tail vein or into a subcutaneous area of mice and the numbers of lung metastatic nodules or the volumes of subcutaneous tumors were assessed. Untreated cells were incubated with PKH26. Experimental metastasis models were then generated and used to assess the fixed cancer cells.. Tumor development in the subcutaneous tumor models and cell viabilities were similar among the four groups. However, the GGA plus hyperthermia group had fewer lung metastatic nodules in the experimental lung metastasis model and higher Hsp70 induction than the other cell groups. The GGA plus hyperthermia pretreatment group also showed a lower number of fixed cells in lungs and lower activation of NF-kappa-B by TNF-alpha than the other cell groups.. It is suggested the metastatic potential but not the proliferation potency of cancer cells is inhibited by the transient induction of Hsp70.

Topics: Animals; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Disease Models, Animal; Diterpenes; HSP70 Heat-Shock Proteins; Hyperthermia, Induced; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; NF-kappa B