| Objective:To investigate the effects of the lanthanum chloride on the growth and apoptosis of cervical cancer cells in vivo as well as the potential molecular mechanism, which will help to provide experimental data for cervical cancer treatment with lanthanum chloride.Methods:Kunming mice were implanted with mice cervical cancer U14 cells to establish tumor-bearing mouse model, which were randomly divided into three groups: control (NS) group, lanthanum chloride (LaCl3) group and cisplatin (DDP) group. There are thirty mice in each group. Continuous administration of lanthanum chloride for 7 days, the daily habits, weights and survivals of the mice were observed. At the end of the experiment, the weights of tumor were measured and tumor inhibition rate were calculated. Apoptosis was detected by TUNEL assay. The expressions of apoptosis-related gene Bcl-2 and Bax of tumor were examined by RT-PCR. The protein expressions of Bcl-2, Bax and Caspase-3 of tumor were detected by immunohistochemistry. The remaining 15 tumor-bearing mice in each group were fed to observe the survival of mice.Results:1. The vigour, diet and defecation of mice were observed. There were no significant differences between Lacl3 group and NS group, but the mice with worse vigour, anorexia, diarrhea, weight loss and so on, were observed in the DDP group.2. LaCl3 can inhibited the cervical cancer subcutaneous tumor growth. The tumor weight of lanthanum chloride group (0.5mg/kg,2mg/kg,8mg/kg) and DDP group were (0.9±0.17)g, (0.73±0.12)g, (0.56±0.11)g, (0.32±0.1)g, respectively, which were significantly lower than that of the control group (1.42±0.30)g(P<0.05); The inhibitory rates of lanthanum chloride groups(0.5mg/kg,2mg/kg,8mg/kg) and DDP group were(36.85±9.20)%,(48.59±9.51)%, (60.16±9.42)%, (77.46±10.12)%. 3. LaCl3 can significantly prolong survival of tumor-bearing mice. The median survival of LaCl3 group (0.5mg/kg,2mg/kg,8mg/kg) were 60,68,46 days, respectively, and NS group was 55 days, but DDP group was 46 days.4. TUNEL assay showed that the cells apoptosis index of LaCl3 (2mg/kg) group, DDP group were (12.53±3.05)%, (13.62±2.97)%, respectively, which were significantly higher than that of the control group (5.38±1.45)%(P<0.05).5. Immunohistochemistry showed that the expression of apoptosis-associated protein The IOD of Bax of LaCl3(2mg/kg) group and DDP group were 53826.54±5534.8, 71453.65±4964.7, respectively, which were significantly higher than that of the NS group 33860.32±4964.78(P<0.05); The IOD of Caspase-3 of LaCl3 (2mg/kg) group and DDP group were 18218.69±2462.2,12128.67±912.91, respectively, which were significantly higher than that of the NS group 4729.93±1188.45 (P<0.05); The IOD of Bcl-2 of LaCl3 (2mg/kg) group and DDP group were 21961.61±1154.22,14613.66±1043.82, respectively, which were significantly higher than that of the NS group 48873.96±3508.15 (P<0.05).6. RT-PCR analysis indicated that the expression of apoptosis-related gene Bcl-2 was decreased by LaCl3 and DDP. On the contrary, the expression of apoptosis-related gene Bax was increased by LaCl3 and DDP. The IOD of Bax/p-actin of LaCl3 (2mg/kg) group and DDP group were 0.70±0.12,0.70±0.13, respectively, which were significantly higher than that of the NS group 0.47±0.04 (P<0.05); The IOD of Bcl-2/β-actin of LaCl3 (2mg/kg) group and DDP group were 0.64±0.07,0.55±0.04, respectively, which were significantly lower than that of the NS group (0.89±0.08,,P<0.05).Conclusion:1. LaCl3 can inhibit the cervical cancer subcutaneous tumor growth significantly.2. LaCl3 improved tumor-bearing mice's living quality.3. LaCl3 can significantly prolong the survival of tumor-bearing mice.4. LaCl3 can induce cervical cancer cells apoptosis.5. LaCl3 can inhibit cervical cancer cells proliferation and induce apoptosis by up-regulating Bax and Caspase-3 expressions and down-regulating Bcl-2 expression. |
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