Qizhu Anti-Cancer Recipe promotes anoikis of hepatocellular carcinoma cells by activating the c-Jun N-terminal kinase pathway
Zhiyi Han,
Qi Huang,
Minling Lv,
Mengqing Ma,
Wei Zhang,
Wenxing Feng,
Rui Hu,
Xinfeng Sun,
Jing Li,
Xin Zhong,
Xiaozhou Zhou
Affiliations
Zhiyi Han
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China
Qi Huang
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China
Minling Lv
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China
Mengqing Ma
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China
Wei Zhang
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China
Wenxing Feng
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China
Rui Hu
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China
Xinfeng Sun
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China
Jing Li
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China
Xin Zhong
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China
Xiaozhou Zhou
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No.1 Fuhua Road, Futian District, Shenzhen, 518000, China; Department of Liver Disease, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China; Corresponding author. Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, No. 1 Fuhua Road, Futian District, Shenzhen, 518000, China.
Background: Qizhu Anti-Cancer Recipe (QACR) is a traditional Chinese medicine widely used in treating several liver diseases. However, its function and the relevant mechanism underlying its effect in treating hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to explore the effect of QACR in HCC, which are expected to be a potential therapeutic scheme for HCC. Materials and methods: The chemical compositions of QACR were determined by liquid chromatography/quadrupole time-of-fight mass spectrometry (LC-QTOF-MS). The anoikis-resistant HCC cell proliferation and angiopoiesis were detected using the cell counting kit 8 (CCK8) assay, trypan blue, calcein AM/EthD-1, flow cytometer, Western blot, and tube formation assays. An orthotopic xenograft mouse model was established to evaluate the in vivo effects of the QACR. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, CD31, caspase-3, caspase-8, caspase-9, PARP-1, DFF40, phospho-c-Jun NH2-terminal kinase (p-JNK), and JNK was assessed using Western blot and immunohistochemical analysis. Results: QACR reduced the growth and tube formation of anoikis-resistant HCC cells and enhanced cell apoptosis in vitro. In the orthotopic xenograft mouse models, QACR suppressed the tumorigenesis of HCC in vivo. Mechanistically, QACR modulated the JNK pathway. The JNK inhibitor (SP600125) reverses the inhibitory effects of QACR on anoikis-resistant HCC cell proliferation and angiopoiesis. Conclusion: Our study suggests that QACR suppresses the proliferation and angiopoiesis of anoikis-resistant HCC cells by activating the JNK pathway. Therefore, QACR is a promising new therapeutic strategy for treating hepatocellular carcinoma.
