Trifluoperazine Activates FOXO1-Related Bax/Bcl-2 Signals to Promote Apoptosis in Hepatocellular Carcinoma
JIANG Jing-wen1, CHEN Xue-wu1*, LUO Rong-cheng2, CAI Hong-bing2, HUANG Zhong-xi3
1. Department of Medical Oncology, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou 570203, China;
2. Department of Medical Oncology, TCM-Integratel Cancer Center of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510310, China;
3. Cancer Research Institute, Southern Medical University, Guangzhou 510515, China
OBJECTIVE To investigate the mechanism of FOXO1-related apoptosis of trifluoperazine(TFP) in hepatocellular carcinoma(HCC). METHODS Cytotoxicity of TFP was observed with CCK8 test. Effect of TFP on cell cycle was observed with flow cytometry(FCM). Immunofluorescence was performed to analyse FoxO1 localisation in SMMC-7721 and Bel-7402 cells. Small interfering RNA (siRNA) was used to transfect SMMC-7721 and Bel-7402 cells. Quantitative real-time polymerase chain reaction and Wstern blots were performed to analyse whether FoxO1 transactivates the Bax/Bcl-2. RESULTS TFP could inhibit the vitality of two cell lines and induce cell cycle arrest at G0/G1. TFP reversed the cytoplasmic localization of FOXO1 to nuclear and increased its expression in nuclear, and increased the ratio of Bax/Bcl-2. Knockdown of FOXO1 significantly abrogated the TFP-induced apoptosis by decreasing the Bax/Bcl-2 expression. TFP in vivo could effectively restrict the angiogenesis and tumor growth with reduced expression of VEGF, Bcl-2, and PCNA, and increased the nuclear localization of FOXO1, which indicated its antitumor role in HCC. CONCLUSION This study shows that TFP can induce apoptosis in hepatocarcinoma cells through the upregulation of Bax/Bcl-2 mediated by nuclear translocation and activation of the transcription factor FOXO1. TFP in vivo could effectively restrict the angiogenesis and tumor growth with reduced expression of VEGF, Bcl-2, and PCNA, and increase the nuclear localization of FOXO1, which indicate its antitumor role in HCC.
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2019, Vol. 54 
