Synergistic antitumor effects of liposomal honokiol combined with cisplatin in colon cancer models
Synergistic antitumor effects of liposomal honokiol combined with cisplatin in colon cancer models
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DOI：
10.3892/ol.2011.350
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发表时间：
2011-09-01
期刊：
影响因子：
2.9
通讯作者：
Ma, Jun Rong
中科院分区：
文献类型：
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作者：
Cheng, Niang;Xia, Tian;Ma, Jun Rong
和诺平是一种新型的抗肿瘤药物，在许多肿瘤细胞系和异种移植模型中可诱导细胞凋亡并抑制血管内皮生长。已经提出，化疗的抗肿瘤作用可以与抗血管生成剂组合作为抗癌策略来增加。在本研究中，我们研究了和厚朴酚的潜力，以增加顺铂（DDP）的抗肿瘤作用时，代理和药物联合在小鼠CT 26结肠癌模型，并探讨了潜在的机制。制备和诺酮脂质体（LH），并以不同剂量给予雌性BALB/c小鼠LH，以确定和诺酮的最佳剂量。采用流式细胞术分析细胞凋亡的评价。采用脂质体包裹和厚朴，以提高其水溶性。LH通过诱导CT 26细胞凋亡抑制CT 26细胞增殖，并显著增强DDP诱导的CT 26细胞凋亡。在体内，LH加DDP的全身给药导致皮下肿瘤生长的抑制超过了单独使用LH或DDP观察到的效果。与单独治疗相比，这种生长减少与细胞凋亡水平升高（TUNEL染色）和内皮细胞密度降低（CD 31染色）相关。总的来说，这些发现表明，LH可能会增加体外和体内CT 26细胞凋亡的诱导，根据协同分析，这种联合治疗在肿瘤进展中表现出协同抑制作用。本研究对进一步探索联合治疗结肠癌的潜在应用具有重要意义。
Honokiol, a novel antitumor agent, may induce apoptosis and inhibit the growth of vascular endothelium in a number of tumor cell lines and xenograft models. It has been proposed that the antitumor effects of chemotherapy may be increased in combination with an antiangiogenesis agent as an anticancer strategy. In the present study, we examined the potential of honokiol to increase the antitumor effect of cisplatin (DDP) when the agent and drug were combined in murine CT26 colon cancer models, and investigated the underlying mechanism. Liposomal honokiol (LH) was prepared, and female BALB/c mice were administered LH at various doses to determine the optimum doses for honokial. Evaluation of cell apoptosis was analyzed using flow cytometry. Honokiol was encapsulated with liposome to improve its water insolubility. In vitro, LH inhibited the proliferation of CT26 cells via apoptosis and significantly enhanced the DPP-induced apoptosis of CT26 cells. In vivo, the systemic administration of LH plus DDP resulted in the inhibition of subcutaneous tumor growth beyond the effects observed with either LH or DDP alone. This growth reduction was associated with elevated levels of apoptosis (TUNEL staining) and reduced endothelial cell density (CD31 staining) compared with either treatment alone. Collectively, these findings indicate that LH may augment the induction of apoptosis in CT26 cells in vitro and in vivo, and this combined treatment has exhibited synergistic suppression in tumor progression according to the synergistic analysis. The present study may be significant to future exploration of the potential application of the combined approach in the treatment of colon cancer.