title: Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil.
abstract: Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α4-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Wan
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Huo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Jichuang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Obstetrics and Gynecology, Fuzhou General Hospital, Fuzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Medicine Oncology, East Hospital of Xiamen University, Fuzhou, China.
authors.forename: Fangwei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Surgery, East Hospital of Xiamen University, Fuzhou, China.
authors.forename: Xiaohuang
authors.initials: X
authors.lastname: Tu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage; D004318:Doxycycline / Q000008:administration & dosage; D004347:Drug Interactions; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008239:Lysine / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015735:Mifepristone; D008239:Lysine; D004318:Doxycycline; D001241:Aspirin
keywords: HAMPT; cancer metastasis; cell adhesion molecules; drug combination; metastasis chemoprevention