[Inhibitory effects of a combination of rmhTRAIL and gemcitabine on human non-small cell lung cancer cell line NCI-H460 cells in vitro and in vivo].
OBJECTIVE
To evaluate the inhibitory effects of recombinant mutant tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) combined with chemotherapeutic agent gemcitabine (GEM) on human lung cancer cell line NCI-H460 cells in vitro and in vivo.


METHODS
MTT was used to evaluate the cytotoxic effects of rmhTRAIL and GEM either used alone or in combination treatment on NCI-H460 cells. BAL B/c nude mice were transplanted with NCI-H460 tumor. The tumor-bearing nude mice were randomly divided into 6 groups (n = 6): negative control group (to be injected intraperitoneally with normal saline); rmhTRAIL group; GEM group; rmhTRAIL plus GEM group; GEM plus DDP group; rmhTRAIL plus GEM andDDP group. The tumor size was measured every 3 - 4 days. Twenty one days after the administration of different drugs the mice were killed and the tumors were taken out and weighed.


RESULTS
The growth inhibition of NCI-H460 cells was dose-dependent after exposure to rmhTRAIL, GEM alone or together. The combination of rmhTRAIL and GEM showed a synergistic inhibitory effect at different concentrations. The relative tumor volume of rmhTRAIL group, rmhTRAIL plus GEM group, GEM plus DDP group and rmhTRAIL plus GEM and DDP group were 4.75 +/- 3.04, 2.53 +/- 1.25, 4.52 +/- 2.87, and 1.69 +/- 0.97, respectively, all significantly smaller than that of the negative control group (8.82 +/- 5.62, P < 0.05 or P < 0.01). The tumor weight of these four groups were (2.23 +/- 0.29) g, (1.12 +/- 0.77) g, (2.51 +/- 0.87) g, and 0.60 +/- 0.18 g, respectively, all significantly less then that of the negative control group (4.71 g +/- 0.97 g, all P < 0.01). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM group were significantly smaller than those of either rmhTRAIL group or GEM group (P < 0.05 and P < 0.01, respectively). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM and DDP group were significantly smaller than those of either rmhTRAIL group or GEM plus DDP group (P < 0.05 and P < 0.01, respectively).


CONCLUSIONS
The combination of rmhTRAIL and GEM has a synergistic inhibitory effect on human NSCLC cell line NCI-H460 cells either in vitro and in vivo.
Tang
Chuan-hao
CH
Lung Cancer Department, Tumor Center of PLA, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
Liu
Xiao-qing
XQ
Yang
Shi-fang
SF
Zhu
Bing
B
Gao
Hong-jun
HJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000008:administration & dosage; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage*; D047368:Tumor Burden / Q000187:drug effects; D000093542:Gemcitabine
D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine