Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we descri...Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we describe a functional product based on a combination of compounds,which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases,improving anti-cancer treatment,and enhancing immunity and antioxidant capacity.Our designed combination,named MVBL,consists of four inexpensive compounds:L-selenium-methylselenocysteine(MSC),D-α-tocopheryl succinic acid(VES),β-carotene(β-Ca),and L-lysine(Lys).Methods:The effects of MVBL on cell viability,cell cycle,cell apoptosis,cell migration,cell invasion,reactive oxygen species(ROS),and paclitaxel(PTX)-combined treatment were studied in vitro.The inhibition of tumor metastasis,antioxidation,and immune enhancement capacity of MVBL were determined in vivo.Results:MVBL exhibited higher toxicity to tumor cells than to normal cells.It did not significantly affect the cell cycle of cancer cells,but increased their apoptosis.Wound healing,adhesion,and transwell assays showed that MVBL significantly inhibited tumor cell migration,adhesion,and invasion.MVBL sensitized MDA-MB-231 breast cancer cells to PTX,indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs.In mice,experimental data showed that MVBL inhibited tumor metastasis,prolonged their survival time,and enhanced their antioxidant capacity and immune function.Conclusions:This study revealed the roles of MVBL in improving immunity and antioxidation,preventing tumor growth,and inhibiting metastasis in vitro and in vivo.MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.展开更多
The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of...The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of a new breakthrough.Cure for cancer post-metastases still seems tantalisingly out of reach.Once metastasized,cancer-related death is extremely difficult,if not impossible,to be reversed.Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer chemoprevention.Deep learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting initiated.We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites.The adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive candidates.The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.展开更多
基金the National Natural Science Foundation of China(Nos.81961138017 and 81703555)the Natural Science Foundation of Fujian Province(Nos.2021J011046 and 2020J01859)+4 种基金the Young and Middle-aged Teacher Education Research Project of Fujian Province(No.JAT200412)the Science and Technology Planning Projects of Fuzhou(No.2021S094)the Science and Technology Planning Projects of Fuzhou Institute of Oceanography(No.2021F08)the Belt&Road Program(No.KXPT-2021-3,CAST)the Ministry of Science and Technology of China(No.2015CB931804)。
文摘Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we describe a functional product based on a combination of compounds,which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases,improving anti-cancer treatment,and enhancing immunity and antioxidant capacity.Our designed combination,named MVBL,consists of four inexpensive compounds:L-selenium-methylselenocysteine(MSC),D-α-tocopheryl succinic acid(VES),β-carotene(β-Ca),and L-lysine(Lys).Methods:The effects of MVBL on cell viability,cell cycle,cell apoptosis,cell migration,cell invasion,reactive oxygen species(ROS),and paclitaxel(PTX)-combined treatment were studied in vitro.The inhibition of tumor metastasis,antioxidation,and immune enhancement capacity of MVBL were determined in vivo.Results:MVBL exhibited higher toxicity to tumor cells than to normal cells.It did not significantly affect the cell cycle of cancer cells,but increased their apoptosis.Wound healing,adhesion,and transwell assays showed that MVBL significantly inhibited tumor cell migration,adhesion,and invasion.MVBL sensitized MDA-MB-231 breast cancer cells to PTX,indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs.In mice,experimental data showed that MVBL inhibited tumor metastasis,prolonged their survival time,and enhanced their antioxidant capacity and immune function.Conclusions:This study revealed the roles of MVBL in improving immunity and antioxidation,preventing tumor growth,and inhibiting metastasis in vitro and in vivo.MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
基金NSFC 81961138017,81773063,82202355 and 3220422101Belt&Road Program,CAST and (2021FZR0101)Natural Science Foundation of Fujian Province(2021J05210,2021J011046).
文摘The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of a new breakthrough.Cure for cancer post-metastases still seems tantalisingly out of reach.Once metastasized,cancer-related death is extremely difficult,if not impossible,to be reversed.Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer chemoprevention.Deep learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting initiated.We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites.The adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive candidates.The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.
