Ai zheng = Aizheng = Chinese journal of cancer · 2007
[Effects of interleukin-12 transfection on proliferation of ovarian cancer SKOV3 cells in vitro and in vivo].
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Wang Jing, Zhang Chang-Qing, Liu Juan, Sui Li-Hua
Аннотация
BACKGROUND & OBJECTIVE: The incidence, recurrence rate, and metastasis rate of malignant ovarian tumors are high. Interleukin-12 (IL-12) has antitumor effect. This study was to investigate the effects of IL-12 on the proliferation of human ovarian carcinoma SKOV3 cells in vitro and in vivo.
METHODS: The plasmid containing mouse IL-12 gene was transfected into SKOV3 cells (SKOV3/IL-12). Blank plasmid-transfected SKOV3 cells (SKOV3/neo) and untransfected SKOV3 cells were used as controls. The expression of IL-12 protein was detected by ELISA. The proliferation inhibition rate and population doubling time (PDT) of SKOV3 cells were evaluated by MTT assay. SKOV3/IL-12, SKOV3/neo and SKOV3 cells were inoculated in nude mice subcutaneously. Tumor growth was recorded. The serum levels of IL-12 and interferon-gamma (IFN-gamma) in mice was detected by ELISA. The expression of vascular endothelial growth factor (VEGF) and IFN-gamma-inducible protein 10 (IP-10), and microvessel density (MVD) in tumor tissues was detected by immunohistochemistry.
RESULTS: After transfection, the protein level of IL-12 was significantly higher in SKOV3/IL-12 cells than in SKOV3/neo and SKOV3 cells [(473.0+/-38.0) pg/ml vs. (16.0+/-1.3) pg/ml and (16.0+/-1.2) pg/ml at 48 h, (522.0+/-32.0) pg/ml vs. (18.0+/-1.6) pg/ml and (17.0+/-1.4) pg/ml at 60 h, P<0.01]. The proliferation inhibition rate of SKOV3/IL-12 cells was significantly higher than those of SKOV3/neo and SKOV3 cells (63.7% vs. 0% and 0%, P<0.01). The PDT was significantly longer in SKOV3/IL-12 cells than in SKOV3/neo and SKOV3 cells [(45.8+/-2.7) h vs. (27.6+/-2.2) h and (28.2+/-2.1) h, P<0.01]. In nude mice, the tumor formation rate of SKOV3/IL-12 cells was lower than those of control cells (5/8 vs. 8/8 and 8/8)û the tumor formation time was significantly longer in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group [(15.0+/-5.0) days vs. (7.9+/-3.2) days and (7.8+/-2.4) days, P<0.01]. The volume and weight of tumors and the body weight of mice were significantly lower in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01). The serum levels of IL-12 and IFN-gamma were significantly higher in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01). The positive rate of VEGF and MVD were significantly lower and the positive rate of IP-10 was higher in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01).
CONCLUSIONS: Transfection of IL-12 can inhibit the proliferation and suppress the tumorigenic ability of SKOV3 cells. IL-12 can promote IFN-gamma to induce IP-10 production, thereafter, inhibit neovascularization in tumors.
METHODS: The plasmid containing mouse IL-12 gene was transfected into SKOV3 cells (SKOV3/IL-12). Blank plasmid-transfected SKOV3 cells (SKOV3/neo) and untransfected SKOV3 cells were used as controls. The expression of IL-12 protein was detected by ELISA. The proliferation inhibition rate and population doubling time (PDT) of SKOV3 cells were evaluated by MTT assay. SKOV3/IL-12, SKOV3/neo and SKOV3 cells were inoculated in nude mice subcutaneously. Tumor growth was recorded. The serum levels of IL-12 and interferon-gamma (IFN-gamma) in mice was detected by ELISA. The expression of vascular endothelial growth factor (VEGF) and IFN-gamma-inducible protein 10 (IP-10), and microvessel density (MVD) in tumor tissues was detected by immunohistochemistry.
RESULTS: After transfection, the protein level of IL-12 was significantly higher in SKOV3/IL-12 cells than in SKOV3/neo and SKOV3 cells [(473.0+/-38.0) pg/ml vs. (16.0+/-1.3) pg/ml and (16.0+/-1.2) pg/ml at 48 h, (522.0+/-32.0) pg/ml vs. (18.0+/-1.6) pg/ml and (17.0+/-1.4) pg/ml at 60 h, P<0.01]. The proliferation inhibition rate of SKOV3/IL-12 cells was significantly higher than those of SKOV3/neo and SKOV3 cells (63.7% vs. 0% and 0%, P<0.01). The PDT was significantly longer in SKOV3/IL-12 cells than in SKOV3/neo and SKOV3 cells [(45.8+/-2.7) h vs. (27.6+/-2.2) h and (28.2+/-2.1) h, P<0.01]. In nude mice, the tumor formation rate of SKOV3/IL-12 cells was lower than those of control cells (5/8 vs. 8/8 and 8/8)û the tumor formation time was significantly longer in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group [(15.0+/-5.0) days vs. (7.9+/-3.2) days and (7.8+/-2.4) days, P<0.01]. The volume and weight of tumors and the body weight of mice were significantly lower in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01). The serum levels of IL-12 and IFN-gamma were significantly higher in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01). The positive rate of VEGF and MVD were significantly lower and the positive rate of IP-10 was higher in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01).
CONCLUSIONS: Transfection of IL-12 can inhibit the proliferation and suppress the tumorigenic ability of SKOV3 cells. IL-12 can promote IFN-gamma to induce IP-10 production, thereafter, inhibit neovascularization in tumors.