Introduction. Peritoneal metastasis is a frequently occurring complication patients with gastrointestinal, pancreatic, ovarian cancers and is a condition difficult to manage, clinically, due largely to the lack of effective treatment. In the present study, we report an accidental and novel discovery that the extract of Yangzheng Xiaoji (YZXJ), a traditional medical formula used in cancer treatment had an anti-peritoneal metastasis function.
Materials and methods. Human primary cultured peritoneal mesothelial cells were used as an in vitro cellular model. Human gastric, colorectal, pancreatic, ovarian and prostate cancer cells were used in the tests. Tumour-mesothelial interaction, invasion and migration were assessed with YZXJ. Athymic nude mice peritoneal metastasis model was used to evaluate the effects in vivo.
Results. Soluble YZXJ was firstly extracted in a highly reproducible manner. YZXJ extract (DME25) had a negletable toxicity to cancer cells and mesothelial cells. However, it profoundly inhibited the tumour-mesothelial adhesions in the type of tumour cells tested with pancreatic and colorectal cancer cells amongst the most sensitive ones to YZXJ (p<0.001), a phenomenon seen with a number of cell based assays. The inhibitory effect was also seen with cellular migration. A similar pattern of inhibition was seen on tumour adhesion to hyaluronan (HA) coated surface. It was further revealed that YZXJ and an hyaluronan inhibitor and anti-CD44 antibodies had additive effects with YZXJ on tumour-mesothelial interactions. YZXJ extract had an inhibitory effect on the phosphorylation of SRC kinase in cancer cells and in mesothelial cells as shown by Western blotting and immunofluorescence microscopy. In the peritoneal metastasis in vivo model, it was demonstrated that intraperitoneal administration of YZXJ significantly reduced the formation of metastatic nodules (p=0.035, control vs YZXJ treatment). This was seen with little side effects. We have also shown that hyaluronan inhibitor strengthened the inhibitory effect exerted by YZXJ.
Conclusion. Yangzheng Xiaoji has an potent inhibitory effect on tumour-mesothelial interactions of a variety of tumour types and also markedly reduces the peritoneal metastasis in vivo. This effect is likely to be achieved by its effect on the SRC signalling pathway. Yangzheng Xiaoji presents a new way of treating peritoneal metastasis.
Citation Format: Wen G. Jiang, Yongning Jia, Lin Ye, Ke Ji, Yong Gao, Cong Wei, Yiling Wu, Nick Topley, Anna Kift-Morgan, Jiafu Ji. The anti-peritoneal metastasis properties of Yangzheng Xiaoji, the potential role of hyaluronan and CD44. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4034. doi:10.1158/1538-7445.AM2014-4034