Dong Lan-feng, Zhang Ying-jun, Liu Jing-sheng, Song Shu-xia, Hou Jie, Lu Zhan-jun
Experiment Animal Department, Hebei Medical University, Shijiazhuang 050017, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2006 Jul;22(4):458-62.
To observe the synergic action of monkshood polysaccharide (MPS) and adriamycin (ADM) long circulating temperature-sensitive liposome (ALTSL) in targeting therapy for H22 tumor-bearing mice and explore the mechanism.
The anti-tumor activity was evaluated by using the tumor's weight as an index. The life prolongation rate of mice was calculated according to the survival time of the tumor-bearing mice. The killer activity of NK cells and the lymphocyte transformation rate were detected by the LDH release assay and MTT colorimetry, respectively. The apoptosis of tumor cells and the expressions of p53, Fas, Fas-L and caspase-3 were analyzed by flow cytometry. The expressions of IL-2 mRNA and IL-12 mRNA in spleen lymphocytes were determined by RT-PCR. The pathologic changes of tumor, heart, liver and kidney tissues of the tumor-bearing mice were observed under light microscope.
Compared with the adriamycin liposome group, the anti-tumor effects were enhanced in (MPS+ALTSL) group with tumor growth inhibitory rate up to 80.4%. The survival time of the tumor-bearing mice in ALTSL and (MPS+ALTSL) groups was significantly prolonged compared with the ADM group (P<0.01). The killer activity of NK cells was higher in ALTSL group than in the NS and ADM groups, and was highest in (MPS+ALTSL) group. The lymphocyte transformation rate of (MPS+ALTSL) group was markedly increased (P<0.01) as compared with the ADM group. The result of RT-PCR indicated that the expressions of IL-2 mRNA and IL-12 mRNA in lymphocytes in the adriamycin long circulating liposome (ALCL) group were significantly higher than those in the ADM group. Expressions of IL-2 mRNA and IL-12 mRNA was much higher in (MPS+ALTSL) group than in ALTSL group. The pathological examination indicated that in (MPS+ALTSL) group, more lymphocytes and monocytes were found in tumor tissue.
ALTSL can increase the anti-tumor effect and decrease the side-effects (such as the cytotoxicity) of ADM. MPS combined with ALTSL can enhance killer activity of NK cells and transformation of T cells, supporting their synergic anti-tumor effect.
观察附子多糖（MPS）与阿霉素（ADM）长循环热敏脂质体（ALTSL）对H22荷瘤小鼠靶向治疗的协同作用并探讨其机制。
以肿瘤重量为指标评价抗肿瘤活性。根据荷瘤小鼠的生存时间计算小鼠的生命延长率。分别采用乳酸脱氢酶释放法和MTT比色法检测NK细胞的杀伤活性和淋巴细胞转化率。采用流式细胞术分析肿瘤细胞凋亡及p53、Fas、Fas-L和caspase-3的表达。采用RT-PCR法检测脾淋巴细胞中IL-2 mRNA和IL-12 mRNA的表达。光镜下观察荷瘤小鼠肿瘤、心脏、肝脏和肾脏组织的病理变化。
与阿霉素脂质体组相比，（MPS+ALTSL）组抗肿瘤作用增强，肿瘤生长抑制率达80.4%。与ADM组相比，ALTSL组和（MPS+ALTSL）组荷瘤小鼠的生存时间显著延长（P<0.01）。ALTSL组NK细胞的杀伤活性高于NS组和ADM组，（MPS+ALTSL）组最高。与ADM组相比，（MPS+ALTSL）组淋巴细胞转化率明显升高（P<0.01）。RT-PCR结果显示，阿霉素长循环脂质体（ALCL）组淋巴细胞中IL-2 mRNA和IL-12 mRNA的表达明显高于ADM组。（MPS+ALTSL）组IL-2 mRNA和IL-12 mRNA的表达高于ALTSL组。病理检查表明，（MPS+ALTSL）组肿瘤组织中淋巴细胞和单核细胞增多。
ALTSL可增强阿霉素的抗肿瘤作用，降低其毒副作用（如细胞毒性）。MPS联合ALTSL可增强NK细胞的杀伤活性和T细胞的转化，发挥协同抗肿瘤作用。
