Combining thioridazine and loratadine for the treatment of gastrointestinal tumor

Chen,Tingting; Hu,Yunlong; Liu,Bin; Huang,Xinping; Li,Qin; Gao,Ningning; Jin,Zhenchao; Jia,Tieliu; Guo,Deyin; Jin,Guangyi

doi:10.3892/ol.2017.6815

Combining thioridazine and loratadine for the treatment of gastrointestinal tumor

Authors:
- Tingting Chen
- Yunlong Hu
- Bin Liu
- Xinping Huang
- Qin Li
- Ningning Gao
- Zhenchao Jin
- Tieliu Jia
- Deyin Guo
- Guangyi Jin
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Affiliations: Cancer Research Center, Department of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China, Department of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: August 24, 2017 https://doi.org/10.3892/ol.2017.6815
Pages: 4573-4580
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 promising therapy for gastrointestinal cancer.

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