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Application of highly eﬃcient and lowly toxic bufadienolides screened from T toad skin in lymphatic chemotherapy for colorectal cancer through a lymphatic metastatic model
Changzheng Hea,1, Zhenyu Zoub,1, Shaoyou Xiaa,1, Xiaowei Xinga,1, Shidong Hua, Zilong Huc, Yuxuan Lia, Songyan Lia, Hongliang Zhanga, Yu Yanga, Yichen Liua, Xiaolei Xua, Boyan Liua, Yufeng Wangd, Yingxin Xue, , Xiaohui Dua,
a Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
b Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, PR China
c Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
d Department of Patient Admission Management, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
e Institute of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
Lymph node metastasis
Background: Lymph node metastasis (LNM) remains a major obstacle to treat colorectal cancer (CRC). Increasing evidences have suggested that bufadienolides contain several fractions displaying antitumor activity and may be applied in lymphatic chemotherapy. However, eﬀects of the highly eﬃcient and lowly toxic (HELT) bufadie-nolides on CRC in lymphatic chemotherapy have not been reported.
Methods: Adenosine triphosphate tumor chemosensitivity assays (ATP-TCA) was performed to detect the in-hibition rate (IR) of fractions of bufadienolides to cytokine-induced killer (CIK) cells and tumor cells. HELT fraction-loaded emulsions of diﬀerent concentrations were prepared. Nude mouse bearing HCT116 tumors in footpad received high-dose emulsion (HD-E), middle-dose emulsion (MD-E), low-dose emulsion (LD-E), control emulsion (CE), Cinobufacini Injection (CI), or normal saline (NS), respectively. Hematoxylin and eosin (H&E) staining, Flow Cytometry (FCM), enzyme-linked immune sorbent assay (ELISA) and hematological examination were applied to evaluate therapeutic eﬀects and potential toxicity.