| IntroductionIn recent decades, changes in cancer-related genes, especially cancer-associated carbohydrate antigens aberration have been paid attentions. But little is known about the sugar-conjugates on the surface of th cells which has been found in early researchs. Galectin-9 is a member of galectin family members, belongs to animal lectins. Galectin-9 is isolated as a tandem-repeat type galectin having two CRDs with selective affinity toβ-galactoside. Like other galectins, galectin-9 exhibits lactose-binding activity and is believes to be involved in cell-cell or cell-matrix interactions. Galectin-9 exhibits a variety of biological functions, such as cell aggregation, adhesion, proliferation and cell apoptosis and modulation of inflammation.The research of the relation between galectin-9 and carcinoma has just started, it is reported that galectin-9 induces breast carcinoma cell apoptosis and aggregation in vitro. And the expression of galectin-9 reduces adhesion of breast cancer cell to extracellular matrix proteins and the expression of galectin-9 in breast cancer tissue is related to prognosis. The same conclusion also been found in human melanoma cell, galectin-9 protein induce the melanoma cell apoptosis and aggregation in vitro. The expression of galectin-9 during the early stage of melanoma such as melanoma in situ is decreased suggesting that the lack of galectin-9 expression is also directly or indirectly involved in the transformation from normal cells to malignant cells. Malignant tumors have all kinds of clinical manifestation and have characteristic expressions themselves, though galectin-9 has antitumor effects we needs a lot of experimental evidences before clinical applications.Cervical cancer has clear precancerous lesions, such as cervical intraepithelial lesions, the carcinogenesis of cervical cancer is a consecutive graded process. It is favorable for us to study about the relation between galectin-9 and carcinogenesis. So we observed the antitumor effects of galectin-9 protein both in vitro and in the cancer cell planted mice. On this basis, we collected the tissues and serums from normal cervical patients, CIN and cervical cancer patients, and proved the differences of galectin-9 expression and analysis their clinical manifestation.Methods1. Cultured Meth A, MM-RU and KATO-III cell lines with null galectin-9 protein together, and observes the medicine-dependent cellular cytotoxicity reaction by WST-1 method. Then observed the induced cancer cell apoptosis by FACS and counting the particles by microscope to evaluate the aggregation of cancer cells.2. Transplant Meth A cell to the subcutaneous tissue and intra-peritoneal of normal mice (C57BL/6J and BABL/c) and nude mice, respectively. To compared the size of the tumor and the survival rate of each mice group.3. Collected normal cervix, CIN and cervical cancer tissues and the serum from these patients and detect the expression of galectin-9 by S-ABC immunohistochemisrty and ELISA methods. To compared the relationship between galectin-9 and carcinogenesis.Results1. In vitro, null galectin-9 protein significantly inhibited the growth of tumor cells. Along with an increase in concentration and time, inhibition role is more and more strong. Galectin-9 protein can also promote the tumor cell apoptosis and aggregation.2. Given null galectin-9 protein by both intravenous and intra-peritoneal administration can inhibit tumor growth of the normal mice, which was transplant with tumor cells, but galectin-9 protein cannot inhibit the growth of tumor or extent the survival rate in nude mice. So it is clear that antitumor effects of galectin-9 need the immune system of the lively mice to inhibit tumor, and we can speculated that galectin-9 protein inhibit tumor by enhance immune system functions. We also find that along with an increase in concentration and time, inhibition role is more and more strong.3. Galectin-9 was evidently detected in normal epithelium and endocervical glands, but in CIN and cervical cancer was significant lower than that in LSIL, suggesting their association with malignant transformation. Galectin-9 in well differentiated cervical cancer was significantly high compared to those in HSIL. Those in cervical cancer were inversely correlated with the grade of differentiation. We found that the immune activity of galectin-9 in the cytoplasm in normal cervical epithelial, but in the nuclear and on the member of CIN even cervical cancer cells.4. ELISA test showed the similar results to immunohistochemistry, galectin-9 potent expression in normal patients and lower in CIN and weak in cervical cancer patients. Serum concentrations of galectin-9 in normal patients is 27.15±14.36pg/ml, CIN group is 21.20±7.74pg/ml and cervical cancer group is 17.43±6.26pg/ml. There is a statistically significant difference among all the groups.Conclusion1. Null galectin-9 protein can inhibit the growth of cancer cell, promote cancer apoptosis and cell aggregation in vitro, by this way galectin-9 maybe can act as antitumor medicine.2. Galectin-9 can inhibit the growth of tumor and extent the survival rate of mice in the case of the integrity of immune system. Galectin-9 can improve the immune ability of mice transplanted with tumor cell to inhibit tumor.3. Galectin-9 expression is decreased gradually with the cervical cancer transformation. |
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