[Effects of suramin in combination with cisplatin on growth and metastasis of lung adenocarcinoma xenografts in mice].
OBJECTIVE
Recent study found angiogenesis plays some important roles in tumor growth and metastasis. This study was to explore the inhibitory effect of angiogenesis inhibitor Suramin in combination with cisplatin (DDP) on the growth and lung metastasis of lung adenocarcinoma LA795 cell xenografts in mice.


METHODS
Highly metastatic LA795 cells were inoculated into the mammary fatty pad of 32 T739 mice to establish lung adenocarcinoma models. Four days after inoculation, the mice were randomized into 4 groups: the mice in control group received intraperitoneal injection of 0.2 ml normal saline everyday; the mice in DDP group received injection of DDP [2 mg. (kg.day)-1] at the 4th, 11th, and 18th days; the mice in Suramin group received injection of Suramin [10 mg. (kg.day)-1] everyday; the mice in combination group received injection of DDP [2 mg. (kg.day)-1] at the 4th, 11th, and 18th days, and Suramin [10 mg. (kg day)-1] everyday. All mice were killed 24 days later. Lung and subcutaneous tumors were examined histologically. The metastatic tumor foci on lung surface were observed, lung weight was measured, the occurrence rate of lung metastasis and the inhibitory rate of metastatic foci were calculated, subcutaneous tumor microvessel density (MVD), vascular endothelial growth factor (VEGF), and nuclear factor-kappaB (NF-kappaB) were determined by immunohistochemistry, and tumor cell apoptosis was measured by TUNEL method.


RESULTS
In DDP, Suramin, and combination groups, tumor growth was suppressed significantly, with growth inhibitory rates of 23.0%, 34.4%, and 56.3%, respectively (P<0.05). Necrosis and decrease of tumor vessels were observed in Suramin and combination groups. The expression of NF-kappaB was significantly lower and tumor cell apoptosis index was significantly higher in DDP, Suramin, and combination groups than in control group (P<0.01). The metastatic foci on lung surface were less in Suramin and combination groups than in DDP and control groups. The expression of MVD and VEGF in subcutaneous tumors and the occurrence rate of lung metastasis were also obviously lower in Suramin and combination groups.


CONCLUSIONS
Suramin has synergetic inhibitory effect with DDP on growth and metastasis of lung adenocarcinoma LA795 cell xenografts in mice through inhibiting angiogenesis and inducing cell apoptosis.
Zhang
Ping
P
Department of Respiratory Medicine, The First Affiliated Hospital, Nanhua University, Hengyang, Hunan 421001, P. R. China. zp9707@sohu.com
He
Jian-Bin
JB
Ou
Li-Wen
LW
Wang
Xiao-Hua
XH
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011897:Random Allocation; D013498:Suramin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D013498:Suramin; D002945:Cisplatin