[Therapeutic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand on non-small lung cell cancer: an experimental with rats].
OBJECTIVE
To evaluate the therapeutic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) on non-small cell cancer (NSCLC).


METHODS
NSCLC cells of the line NCI-H460 were cultured and underwent agarose gel electrophoresis. rmhTRAIL of different concentrations was added into the culture fluid to observe the influence of rmhTRAIL. Nude BALB/c rats were transplanted with rat NCI-H460 tumor. Then the rats carrying xenografts were randomly divided into 5 groups of 8 rats: negative control group to be injected intraperitoneally with normal saline; positive control group to be injected with vancristine; low-dose rmhTRAIL group, to be injected with 1.7 mg/kg rmhTRAIL, middle-dose rmhTRAIL group to be injected with rmhTRAIL 5.0 mg/kg, and high-dose rmhTRAIL group to be injected with 15.0 mg/kg rmhTRAIL. The size of tumor was measured every 3 approximately 4 days. Ten days after the administration of different drugs the rats were killed and the tumors were taken out to undergo TUNEL staining for microscopy.


RESULTS
The relative tumor volume of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 3.19 +/- 2.05 and 1.47 +/- 0.77 respectively, both significantly smaller than that of the negative group (8.48 +/- 5.87, P < 0.05 and P < 0.01). The relative tumor growth rate of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 37.6% and 17.3% respectively. The tumor weight of low-dose rmhTRAIL group and high-dose rmhTRAIL group were 1.09 g +/- 0.55 g and 0.31 g +/- 0.09 g respectively, both significantly lighter than that of the negative control group (2.78 +/- 0.77, both P < 0.01). Large amount of apoptotic cells were seen in the tumor tissues of the rmhTRAIL -treated rats and tumors cells cultured with rmhTRAIL. Agarose gel electrophoresis showed apoptosis-characteristic ladder in the DNA extracted from the rmhTRAIL -treated tumors cells.


CONCLUSIONS
rmhTRAIL dose-dependently inhibit the growth of NSCLC cells, primarily by inducing apoptosis of tumor cells.
Tang
Yan-min
YM
Beijing Sunbio Biotech Co Ltd, Beijing 100081, China.
Yang
Shi-fang
SF
Zhu
Bing
B
Cui
Jun-sheng
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D005260:Female; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use*
D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human