The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway plays a significant role in colorectal adenocarcinoma. NVP-BEZ235 (dactolisib) is a novel dual inhibitor of PI3K/mTOR. The effects of NVP-BEZ235 in human colorectal adenocarcinoma are still unclear. In the present study, we aimed to explore the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells. HT-29 human colorectal adenocarcinoma cells were treated with NVP-BEZ235 (0, 0.001, 0.01, 0.1, 1 and 3 µM) for 24 and 48 h, respectively. Cells were also treated with NVP-BEZ235 (0.1 µM), DDP (100, 300 and 1,000 µM), and NVP-BEZ235 (0.1 µM) combined with DDP (100, 300 and 1,000 µM) respectively, and cultured for 24 h after treatment. MTT assay was utilized to evaluate the effects of NVP-BEZ235 alone or NVP-BEZ235 combined with cis-diamminedichloroplatinum (DDP) on proliferation of HT-29 cells. Cell wound-scratch assay was used detect cell migration. In addition, expression of microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B and LC3B) in HT-29 cells was detected by immunofluorescence at 48 h after NVP-BEZ235 (1 µM) treatment. Expression of proteins involved in cell cycle and proliferation (p-Akt, p-mTOR and cyclin D1), apoptosis (cleaved caspase-3), and autophagy (cleaved LC3B and Beclin-1) were detected by western blot analysis. NVP-BEZ235 inhibited the proliferation and migration of HT-29 human colorectal adenocarcinoma cells. NVP-BEZ235 decreased protein expression of p-Akt, p-mTOR and cyclin D1, and increased protein expression of cleaved caspase-3, cleaved LC3B and Beclin-1 as the concentrations and the incubation time of NVP-BEZ235 increased. In addition, NVP-BEZ235 and DDP had synergic effects in inhibiting cell proliferation and migration. The expression of protein involved in apoptosis (cleaved caspase-3) was higher in drug combination group compared to the NVP-BEZ235 single treatment group. NVP-BEZ235 inhibited the proliferation and migration, and induced apoptosis and autophagy of HT-29 human colorectal adenocarcinoma cells.

Nonalcoholic steatohepatitis (NASH) is characterized by massive lipid deposition in hepatocytes and is often associated with hepatic inflammation and other severe metabolic syndromes. The intervention of NASH can prevent its further progression into hepatocarcinoma. In this study we have successfully constructed liver‐targeted Ce‐based hollow mesoporous nanocarriers loaded with bioactive drugs. This may provide an effective approach for eliminating NASH. Liver‐section‐specific targeting was realized by covalently linked galactose (Gal), which can be specifically recognized by receptors in the membranes of hepatocytes. Meanwhile, resveratrol (Res), a drug used to treat NASH, was efficiently loaded into the pores and cavity of CeO2 (Res@H−CeO2−Gal). In steatotic HepG2 cells (free fatty acid induction), this nanosystem was found to enhance cellular Res internalization for improved anti‐lipogenesis activity. In mice with NASH, Res@H−CeO2−Gal increased Res delivery to liver sections for a reduction in lipid accumulation and enhanced anti‐inflammatory activity from the antioxidant capacity of Ce‐based nanocarriers. This effectively recovered NASH mice to the normal state. These findings show that the hepatic targeting and Res delivery nanoplatform could act as a safe and promising strategy for the elimination of NASH and other liver diseases.