Anti-tumor effects of 13-cis-retinoic acid combined with interferon α-2b in animal model of mantle cell lymphoma
10.3760/cma.j.issn.0253-2727.2016.09.011
- VernacularTitle:13-顺式维甲酸联合IFN-α-2b治疗套细胞淋巴瘤的动物实验研究
- Author:
Jingjing WEN
1
;
Zhibin LIU
;
Caigang XU
Author Information
1. 四川省绵阳市中心医院血液科
- Keywords:
Jeko-1 cell;
Severe Combined Immunodeficiency;
Lymphoma,B-cell;
Tretinoin;
Interferon-alpha
- From:
Chinese Journal of Hematology
2016;37(9):784-789
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the anti-tumor effects of 13-cis-retinoic acid (13eRA) combined with interferonα-2b (IFNα-2b)in mantle cell lymphoma (MCL) animal model.Methods The animal model of MCL was established by introducing Jeko-1 cell line into severe combined immunodeficiency disease mice.The successfully tumor-developed mice were assigned to different groups treated with negative control group (solvents),13cRA (high dose:200mg/kg;middle dose:100mg/kg;low dose:50 mg/kg)alone,IFNα-2b alone or combination of different dose of 13cRA with IFNα-2b,and positive control group (bortezomib,rituximab,cyclophosphamide),respectively.Variations of tumor volume were observed regularly.The relative tumor proliferation rate and tumor inhibition rate were calculated.Immunohistochemistry stain was used to detect the Ki-67 expression and TUNEL was applied to measure the apoptosis of tumor cells.Furthermore,the levels of Cyclin D1,caspase 9 and Rb protein were measured by Western-blot method.Results ① The relative tumor proliferation rates (T/C％)were 30％,37％,32％ and 33％ in middle dose,high dose groups of 13cRA as well as their combination with IFN α-2b,respectively.② Comparing with the negative control,both 13cRA at different doses and its combination with IFNα-2b remarkably inhibited the tumor growth (P＜0.05),while no statistic significance existed in different dose group of 13cRA.IFN-α 2b alone didn't demonstrate the tumor-inhibition effects (P＞0.05).Middle dose of 13cRA and its combination with IFN-α-2b demonstrated relatively high tumorinhibition effects (59.2％ and 62.6％ respectively),which were similar to the effects in positive control (69.4％).③ There was no statistic difference of Ki-67 in each experimental group.④ Comparing with negative control group,all doses of 13cRA and their combinations with IFNα-2b remarkably increased the apoptosis (P＜0.05),similar to the positive control group (P＞0.05).However,IFNα-2b alone didn' t promote the apoptosis of tumor tissue (P=0.098).⑤ Comparing with negative control group,IFNα-2b combined with each dose of 13cRA significantly decreased the levels of cycling D1 and procaspase-9,while increased the level of cleaved caspase-9 (P＜0.05),which were similar to the positive control group (P＞0.05).Nevertheless,13cRA alone didn't demonstrate such effects.Conclusion In the MCL animal model,IFNα-2b alone showed no effects,but combined with IFNα-2b,13cRA displayed anti-tumor effects at different doses.The anti-tumor mechanism of 13cRA combined with IFNα-2b was probably downregulation of the cyclin D1 expression,inhibition of cell proliferation and induction of apoptosis by activating caspase-9.
