Nanomedicine strategies for sustained,controlled,and targeted treatment of cancer stem cells of the digestive system

Cancer stem cells(CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability.They have been identified in a variety of tumors,including tumors of the digestive system.CSCs exhibit some unique characteristics,which are responsible for cancer metastasis and recurrence.Consequently,the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy.Several potential approaches to target CSCs of the digestive system have been explored,including targeting CSC surface markers and signaling pathways,inducing the differentiation of CSCs,altering the tumor microenvironment or niche,and inhibiting ATP-driven efflux transporters.However,conventional therapies may not successfully eradicate CSCs owing to various problems,including poor solubility,stability,rapid clearance,poor cellular uptake,and unacceptable cytotoxicity.Nanomedicine strategies,which include drug,gene,targeted,and combinational delivery,could solve these problems and significantly improve the therapeutic index.This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

WM130 preferentially inhibits hepatic cancer stem-like cells by suppressing AKT/GSK3β/β-catenin signaling pathway

OBJECTIVE The eradication of cancer stem cells(CSCs) is signifcant for cancer therapy and prevention.METHODS In this study,we evaluated WM130,a novel derivative of matrine,for its effect on CSCs using human hepatocellular carcinoma(HCC) cell lines,their sphere cells,and sorted EpCAM+cells.RESULTS We revealed that WM130 could not only inhibit proliferation and colony formation of HCC cells,but also suppress the expression of some stemness-related genes and up-regulate some mature hepatocyte marker genes,indicating a promotion of differentiation from CSCs to hepatocytes.WM130 also suppressed the proliferation of doxorubicin-resistant hepatoma cells,and markedly reduced the cells with CSC biomarker EpCAM.Moreover,WM130 suppressed HCC spheres,not only primary spheres but also subsequent spheres,indicating an inhibitory effect on self-renewal capability of CSCs.Interestingly,WM130 exhibiteda remarkable inhibitory preference on HCC spheres and EpCAM+cells rather than their parental HCC cells and EpCAM-cells respectively.In vivo,WM130 inhibited HCC xenograft growth,decreased the number of sphere-forming cells,and remarkably decreased the levels of EpCAM mRNA and protein in tumor xenografts.Better inhibitory effect was achieved by WM130 in combination with doxorubicin.Further mechanism study revealed that WM130 inhibited AKT/GSK3β/β-catenin signaling pathway.CONCLUSION Collectively,our results suggest that WM130 remark.ably inhibits hepatic CSCs,and this effect may via the down-regulation of the AKT/GSK3β/β-catenin pathway.These findings provide a strong rationale for the use of WM130 as a novel drug candidate in HCC therapy.