Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.

Microcystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture system was established using CRC cells and M2 macrophages in a Transwell chamber. The study found that MC-LR promotes CRC cell migration by upregulating TGF-β1 expression and secretion in M2 macrophages and downregulating CST3 in CRC cells. Neutralizing TGF-β1 increased CST3 expression in CRC cells, while overexpressing CST3 in CRC cells suppressed TGF-β1 expression in M2 macrophages, both of which weakened MC-LR-induced cellular motility in the co-culture system. In vivo, the mice in the MC-LR/AOM/DSS group had more tumor nodules, deeper tumor invasion, and higher M2 macrophage infiltration compared to the AOM/DSS group, and the expression of TGF-β1 and CST3 in tumors was consistent with the cellular level. Overall, this study provides insights into the regulatory mechanism of MC-LR on TME, revealing that MC-LR upregulates the expression and secretion of TGF-β1 in M2 macrophages, which in turn inhibits the expression of CST3 in CRC cells to promote migration.

The present study aimed to explore whether microcystin‑LR (MC‑LR; a well‑known cyanobacterial toxin produced in eutrophic lakes or reservoirs) induced tumor progression by activating cadherin‑11(CDH11). A previous tumor metastasis PCR array demonstrated that MC‑LR exposure resulted in a significant increase in the expression of CDH11. In the present study, to confirm the effect of the MC‑LR treatment on CDH11 expression, HT‑29 cell migration and invasion following MC‑LR treatment were tested by Transwell assays, and protein levels of CDH11 were tested by immunofluorescence and western blot analysis. The results demonstrated that MC‑LR activated CDH11 expression in addition to cell migration and invasion in HT‑29 cells. To further investigate the association between MC‑LR‑induced CDH11 upregulation, and higher motility and invasiveness in HT‑29 cells, knockdown of CDH11 using small interfering RNA (siRNA) in HT‑29 cells was performed. Subsequent Transwell assays confirmed that MC‑LR‑induced enhancement of migration and invasion was significantly decreased following CDH11 knockdown by CDH11‑siRNA in HT‑29 cells. The results from the present study indicate that MC‑LR may act as a CDH11 activator to promote HT‑29 cell migration and invasion.