Ebrahimpour Soheil, Tabari Mohaddeseh Abouhosseini, Youssefi Mohammad Reza, Aghajanzadeh Hamid, Behzadi Manijeh Yousefi
Infection Disease and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran.
Pharmacognosy Res. 2013 Jul;5(3):189-94. doi: 10.4103/0974-8490.112426.
Garlic, a medicinal plant, and Naltrexone (NTX), an opioid receptor antagonist, both have immunomodulatory and antitumor effects. Current study was designed to evaluate synergistic antitumor effects of aged garlic extract (AGE) and NTX.
WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into right flank of 80 BALB/c mice at age of 8 weeks. Mice were randomly categorized in four separate groups: The first group received AGE (100 mg/kg, i.p.), the second group received NTX (0.5 mg/kg, i.p.), the third group received both of them, and the fourth group received phosphate buffered saline as control group. Treatments were administered three times per week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flowcytometery. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) cytokines were measured. All statistical analyses were conducted with SPSS 16 software and P < 0.05 was considered to be statistically significant.
The mice who received AGE+NTX had significantly longer survival time compared with the mice treated with AGE or NTX alone. An enhanced inhibitory effect on tumor growth was seen in combination therapy group. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE+NTX and NTX groups. WEHI-164 specific cytotoxicity of splenocytes was also significantly increased at 25:1 E:T ratio in AGE+NTX treated mice. Coadministration of AGE with NTX resulted in improvement of immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice.
AGE showed synergistic effects with NTX on inhibition of tumor growth and increment of survival times.
大蒜作为一种药用植物，与阿片受体拮抗剂纳曲酮（NTX）均具有免疫调节和抗肿瘤作用。本研究旨在评估陈年大蒜提取物（AGE）与NTX的协同抗肿瘤作用。
于第0天将WEHI-164纤维肉瘤细胞皮下接种于80只8周龄BALB/c小鼠的右侧腹部。小鼠随机分为四组：第一组接受AGE（100mg/kg，腹腔注射），第二组接受NTX（0.5mg/kg，腹腔注射），第三组同时接受二者，第四组接受磷酸盐缓冲盐水作为对照组。每周给药三次。测量肿瘤生长情况并记录发病率。使用流式细胞术测定CD4+/CD8+ T细胞亚群。测定脾细胞对WEHI-164细胞的特异性细胞毒性以及体外干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）细胞因子的产生。所有统计分析均使用SPSS 16软件进行，P < 0.05被认为具有统计学意义。
与单独接受AGE或NTX治疗的小鼠相比，接受AGE+NTX的小鼠存活时间显著延长。联合治疗组对肿瘤生长的抑制作用增强。AGE+NTX组和NTX组中脾细胞的CD4+/CD8+比值及体外IFN-γ产生均显著增加。在接受AGE+NTX治疗的小鼠中，当效应细胞与靶细胞比例为25:1时，脾细胞对WEHI-164的特异性细胞毒性也显著增加。AGE与NTX联合给药可改善BALB/c小鼠对实验性植入纤维肉瘤肿瘤的免疫反应。
AGE与NTX在抑制肿瘤生长和延长存活时间方面显示出协同作用。
