BACKGROUND AND OBJECTIVERadiation sensitivity is closely related to tissue oxygen, and rh-endostatin can induce the high level of oxygen content in tumor by "normalizing" tumor angiogenesis which is associated with radiotherapy sensitivity. The aim of this study is to observe the effect of combination of radiotherapy with rh-endostatin in the rats with lung cancer.

METHODSImmediate lewis cancerous ascetic injection method was used to make rats tumors bearing model, then the rats was divided into four groups randomly: group A was treated with saline; group B was treated with rh-endostatin; group C was treated with irradiation and group D was treated with rh-endostatin and irradiation. After all rats were treated, inhibition rates and the tumor growth curve were calculated. Immunohistochemisty was adopted to check the expressions of vascular endothelial growth factor (VEGF) and microvessel density (MVD).

RESULTSCompared with group A, the growth rates of the tumors in the other group were obviously slower, and the tumor weights were significantly different form group A (P < 0.05). Compared with the other groups, the tumor weights of group D were obviously reduced (P < 0.05). Compared with group A, VEGF and MVD of other three groups were reduced (P < 0.05), and group D were significantly cut down.

CONCLUSIONCombination with radiotherapy and rh-endostatin could inhibit the lung cancer significantly in rats. The possible mechanisms are to decrease the expression ofVEGF and inhibit the production of angiogenesis.

Animals ; Carcinoma, Lewis Lung ; drug therapy ; metabolism ; pathology ; radiotherapy ; Endostatins ; therapeutic use ; Female ; Immunohistochemistry ; Lung Neoplasms ; drug therapy ; metabolism ; radiotherapy ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Random Allocation ; Vascular Endothelial Growth Factor A ; metabolism

Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G1 population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.
Animals ; Apoptosis/drug effects ; Carcinoma, Lewis Lung/metabolism/*radiotherapy ; Caspases/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/radiation effects ; Gene Expression ; Lung Neoplasms/metabolism/*radiotherapy ; Mice ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Radiation Tolerance ; *Radiation-Sensitizing Agents ; Research Support, Non-U.S. Gov't ; Sphingosine/*analogs & derivatives/pharmacology/*therapeutic use