The Experimental Investigation Of Recombinant Human Interferon ω On Tumor Cells

Objective: To investigate the effect of interferon(IFN)-ω on tumor cells. Select the sensitive cells to IFN-ω. Evaluate the inhibited effect and the relevant mechanism of proliferation and invasion. Compare the similarities and differences between IFN-co and IFN-α and to make sure if IFN-co can be a substitute or optimization of IFN-α. Methods: Several human tumor cell lines(breast cancer, colon cancer, hepatocellular carcinoma, melanoma, lung cancer, prostatic cancer, gastric carcinoma, leukemia) were cultured in vivro. IFN-co produced in our laboratory or IFN-α sold in drugstore 100-2000U/ml were used to make certain the minimum working concentration. MTT method was used to measure the cells proliferation, Boyden chambers were used to measure the capability of migration and invasion. Gelatin zymography was used to analyse the MMPs secreted by tumor cells. For in vivo studies, one IFN sensitive cell line-hepatocellular carcinoma HepG2 cells 106 were used to implanted s. c. in nude mice. Nude mice bearing tumor were injected para-tumor s. c. with 105 unit IFN-ω or IFN-α once every interval day for 4 weeks. Control groups were injected with PBS. Tumor dimensions were determined by measuring with calipers. When animals were killed, tumor tissues and different organs (lung, liver, spleen and axillary nodes) were immediately removed and fixed in formaldehyde. Metastasis were detected by HE staining. Immunohistochemical technique was used to analyze PCNA expression. The apoptosis of tumor cells were observed by Tunel techniques. Results: IFN-co can significantly inhibit the proliferation of several tumor cells (hepatocellular carcinoma cell line HepG2, lung cancer cell line LH7 and BE1, prostatic cancer cell line PC3, leukemia cell line K562, et al). The inhibiting rate was from 11.2% to 29.9%. IFN can inhibited the cell proliferation at low dosage (500U/ml)in vitro. MMPs are part ofextracellular matrix degrading enzymes that participating in the processes of cell migration and invasion. There were not any difference in MMPs secretion between IFN groups and control group in vitro. In vitro invasive ability of tumor cells were inhibited by IFN through Boyden chember. Tumor dimensions was significantly reduced in IFN groups. HE staining showed that HepG2 cells migrated to axillary nodes but not to other organs. The metastasis of tumor cells in two groups were not different. PCNA expression of tumor tissues were much lower and the apoptosis of tumor cells were increasing significantly than those of control groups. Conlusion: IFN can inhibit the proliferation of several tumor cells at low dosage in vitro and in vivo. It can reduce the expression of PCNA and induce the apoptosis of tumor tissues in nude mice. IFN inhibited the invasion in vitro but didn't show any inhibiting effect on metastasis of HepG2 cells in vivo. The antitumor effect between IFN-ω and IFN-α was similar. Our experiment show that IFN-ω can be a substitute for IFN-α.