Combining thioridazine and loratadine for the treatment of gastrointestinal tumor

被引:18
作者
Chen, Tingting [1 ,2 ]
Hu, Yunlong [1 ,2 ]
Liu, Bin [1 ]
Huang, Xinping [1 ]
Li, Qin [1 ]
Gao, Ningning [1 ]
Jin, Zhenchao [1 ]
Jia, Tieliu [1 ,2 ]
Guo, Deyin [2 ]
Jin, Guangyi [1 ]
机构
[1] Shenzhen Univ, Dept Med, Canc Res Ctr, 3688 Nanhai St, Shenzhen 518060, Guangdong, Peoples R China
[2] Wuhan Univ, Dept Basic Med Sci, 16 Luojiashan Rd, Wuhan 430071, Hubei, Peoples R China
基金
中国博士后科学基金;
关键词
thioridazine; loratadine; antipsychotic drug; gastrointestinal tumor; apoptosis; CANCER STEM-CELLS; PI3K/AKT/MTOR PATHWAY; MAMMALIAN PROTEIN; APOPTOSIS; BRAIN; PHOSPHORYLATION; IDENTIFICATION; PROLIFERATION; NEUROBLASTOMA; ANGIOGENESIS;
D O I
10.3892/ol.2017.6815
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In 2015, the American Society of Clinical Oncology announced that strategies of using combination therapies have been indicated to be effective against many types of cancer. In the present study, thioridazine (THZ) was used in a combination therapy with loratadine (LOR) to target gastrointestinal tumor, with the aim of investigating whether combined therapy was superior to monotherapy in its antitumor effects. The antiproliferative effects on CT26. WT and MFC cells were analyzed using cell-counting kit-8 assay, and synergistic effect was assessed by combination index (Fig. 1). Annexin V and propidium iodide staining indicated the combination therapy was able to induce apoptosis and that this may be mediated via caspase-3, -9 and poly (ADP-ribose) polymerase (PARP) (Fig. 2). Antitumor activity was also evaluated in CT26. WT xenografts in BALB/c mice (Fig. 3). Furthermore, as expected, combination therapy was able to successfully inhibit the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling pathway (Fig. 4). These findings suggest that the combination therapy with THZ and LOR may provide a promi-sing therapy for gastrointestinal cancer.
引用
收藏
页码:4573 / 4580
页数:8
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